
GenColl 


HSS37 









































































































































































































































































































































































































































































































































































































































































<Y 



a. ® * Ov* 

% y % 

r O * H* -O' 

’ '■ J> ' ^SSMk.''. Hj. * 

^ovt™ 0 ^saEfc . - 1 a^< 




S> cl^ 
S f <? 




cT 3 J T>- 
* <£> J ‘^ 


f; 




o j?<k "'® 1 ||$ ! '° v 0 -^, ”€ 1 ®'° v-°^ 

v°° vl . 0 ys€f^y ., ,v^v t . 



; : & : 

.. \^'/,. „X‘ 

,>►. v * Ta a° * rA^^’/u o < 

.r «» * ^r-, 4 * «> M /'4 o 



o cb'Pp 

w- * <y &ju o * y v> ^ "'j, « 

%'' J «»'\Y ! . >•' •♦° 4 -o'° * t ««, YfY * *l'*,°'V 0 

' \,^° °«^ c 


A-%, o 

> & ■ -Y. " 


£ <J 
**n +* <y 

O ^ ^ * *1 

n ° £ 
* -Jr & 


i/' 

, t> 


Vo* 




° y 

■: ; 

,* 

. - .v*^ °o, 

7 »n * <v 


\*o * ** ^ NO v—o<—A 


ov 
X° V 


•V ..X^^’V 0 

» • ,$. 4 , v vYsW** 9 f> ** 

c^;.«•'^ 



HPB , «wm.i'\^’ 

~ «va J ^IitW o c5>^ o ifMW ~ . 

.w;* # % \®mir' y *■ »^8^* ^ 

V '»»Y \0 Nr 
°o ^ , c ° °*- Y 
; ■ > b-P > o.^sw- -f 

° & ~o '-W/jj 

• . AV»^ 


Vo 


° 

® v 5 ^. - 

« >> 





^'/ Vw*>° V- 

fn* -o’ «.*»> 3 N —V* . <{ * o« vX 

ip> -V _ v jrf^M^lt, ^ V> ♦ rfv Al n < 

^/X 4 ^ a * M’rcf^ ' yk'&'A 9, 


r 
o 

ft ** *V/> ** ^iir : fi^’ n t&'Cr 

'j, uiv^v r » v ~v ^ ' y ^ ^ ; V ,J * 

-• «■ ••** K •:#; K jA: w :tr 

vV 





° ^msik *■ ^ ** 

5& °’ 

'k W °^1&; \c? :® ; V> /^tek*. *W V* /4^B 



*jA^^/h p J * ^U* /V ♦jA^^Alo ^a x3» ^ * N<* cTV * rK\ e*f/h, ° * 

:»; • JwlU *# : mem% v^ *®®a* *«/A« 

•* « . s-««P_ * ¥/ 5 v 2 T 3 N$\Y "• V >>. *■* , $~~»!**ir^ n -C»JV 



c 3'Jj> o 
* y ri, 


V^^T* “So"'"# 

oisq* s * liiyi^ 7 ° 



*rswv„:>mi/::s^Yy^<^ 

?M\s&t\\stM\sftf\\sYat; 

= liHf .- *V A C Hwi? " o fH# - .^ x - « -s^ * - 

V.v V 


x W “ tgi!®® ’ J i‘ c > V - CPU % V'V' r ■'’><• 

°«bv? • .Hfe; S-d*° (&M^\ +o£ \<? :rak - ^ ' 


,o»c> 


V-cr 

* €m§; * ^Cnc3 * S4 o O ®Mil * ^rcf= * o 



>11 0 








EPA 600/R-08/062 | May 2008 | www.epa.gov/ord 


vvEPA 

United States 
Environmental Protection 
Agency 


Scientific and Ethical 
Approaches for 

Observational Exposure Studies 



Office of Research and Development 

National Exposure Research Laboratory 











EPA 600/R-08/062 
May 2008 



Scientific and Ethical Approaches for 
Observational Exposure Studies 


National Exposure Research Laboratory 
Office of Research and Development 
U.S. Environmental Protection Agency 
Research Triangle Park, NC 27711 



Notice 


This document has been subjected to the Agency’s peer and administrative review and has 
been approved for publication as an EPA document. Mention of trade names or commercial 
products does not constitute endorsement or recommendation for use. 


Abstract 


Researchers conduct observational human exposure studies to understand how and the extent 
to which people come into contact with chemicals and environmental stressors in their everyday 
lives, through the air they breathe, the food and liquids they consume, and the things they touch. 
The U.S. Environmental Protection Agency’s (EPA’s) National Exposure Research Laboratory 
(NERL) has conducted observational human exposure studies for several decades and uses the 
information and data from these studies to improve the Agency’s understanding of human 
exposures to chemicals and other stressors and ultimately to support efforts to improve public 
health. Because these studies involve people as research participants, they are complex and raise 
numerous scientific and ethical issues that have to be addressed prior to and during their design 
and implementation. To ensure that EPA’s research continues to be based on the most up-to-date 
science and the highest ethical standards, the Agency has developed this document that contains 
state-of-the-science approaches for conducting observational human exposure studies. This 
document is not meant to represent an official Agency “guidance document” but, rather, serves as 
a resource tool and source of information for NERL and other researchers on which to rely as 
they develop and conduct observational human exposure studies. 


IV 


Foreword 


This document is intended as a resource and reference for the U.S. Environmental Protection 
Agency’s (EPA’s) National Exposure Research Laboratory (NERL) scientists as they develop 
and implement observational human exposure studies. The authors recognize that this document 
also may prove to be useful to others involved in exposure science research, but the document is 
not meant to represent an official Agency “guidance document” and should not be used for that 
purpose. 

Observational human exposure studies involve the collection of information about individuals 
and the environment around them. NERL scientists and managers take the protection of human 
subjects who participate in these studies very seriously. The steps needed to ensure protection of 
the human subjects are often complex, and the specific actions will vary depending on the 
objectives of the study and details about the participants. 

This document does not provide solutions to all scientific and ethical issues that may arise as 
such studies are undertaken. That is, it is not possible to identify or address all potential issues in 
advance or to develop a comprehensive checklist for all such studies. Rather, this document 
attempts to present and discuss the types of issues that will need to be considered and addressed 
as NERL researchers plan and implement observational human exposure studies. The researchers 
will need to work with others—the study team, institutional review board members, EPA’s 
Human Subjects Research Review Official, the participants and their community, and other 
stakeholders—to identify and address all of the relevant issues for their particular study in order 
to ensure that the specific elements of the study will respect, safeguard, and protect the human 
research subjects. 

As EPA employees, NERL scientists face both regulatory and moral obligations to ensure the 
protection of the human subjects participating in observational research. The regulatory 
requirements are set forth in EPA’s human subjects regulations (40 CFR 26). NERL scientists are 
resolved to meet both the “letter” of the law as set forth in the regulations and also the “spirit” 
that derives from the most up-to-date thinking and consensus on these sensitive issues. This 
document provides information on regulatory requirements and the state of the science for a 
number of issues associated with observational human exposure studies to help NERL scientists 
meet their goal of conducting these studies based on the most up-to-date and sound science and 
the highest ethical standards. 

To gather information for the scientific and ethical approaches for observational human 
exposure studies, NERL convened an expert panel workshop on November 28 and 29, 2006, to 
discuss the state of the science. The 11-member panel discussed their ideas for the content of this 
document and the state of the science for various elements of observational human exposure 
studies. The panel agreed that the document planned by EPA should include the following six 
major topic areas: 

(1) identifying elements to be considered in study conceptualization, 

(2) ensuring protection of vulnerable groups, 

(3) addressing privacy and other concerns related to observational human exposure studies, 

(4) creating an appropriate relationship between the participant and investigator. 


v 


(5) building and maintaining appropriate community and stakeholder relationships, and 

(6) designing and implementing strategies for effective communication. 

The structure and content of the current document follow the recommendations of the Expert 
Panel. These recommendations include pragmatic steps that NERL scientists can undertake 
during the development and implementation of observational human exposure studies. 


VI 


Acknowledgments 


This document was developed through the joint efforts of many U.S. Environmental 
Protection Agency (EPA) staff. Roy Fortmann, Larry Cupitt, Kent W. Thomas, and Peter Egeghy, 
researchers in the National Exposure Research Laboratory, were primary authors of the 
document. Linda Sheldon provided input to the development of the document and contributed 
through discussions with the authors on issues associated with observational human exposure 
studies. Davyda Hammond assisted in the revision of the external review draft document. Larry 
Cupitt had primary responsibility for editing the document and coordinating the peer reviews. 
Internal EPA reviewers included Pamela Williams, Warren Lux, Michael Firestone, Gary Bangs, 
Julian Preston, Hugh Tilson, Ronald Williams, Cathy Fehrenbacher, and Deirdre Murphy. The 
EPA Human Studies Review Board, a Federal advisory committee, reviewed the external review 
draft document and provided advice and recommendations that were addressed in the final 
revision of the document. John Barton performed the copy edits of the external review and final 
drafts. Public comments solicited on the external draft were addressed in the final revision of the 
document. 


VII 


Contents 


Notice .iii 

Abstract .iv 

Foreword.v 

Acknowledgments.vii 

Executive Summary.1 

1. Introduction, Purpose, and Scope.7 

1.1. Observational Human Exposure Studies.7 

1.2. Ethical Issues in Observational Human Exposure Studies.8 

1.3. Purpose of This Document.11 

1.4. Process for Developing the Document.13 

1.5. Organization of the Document.13 

2. Elements to Be Considered in Study Conceptualization and Planning.17 

2.1. Scientific Value of a Proposed Observational Human Exposure Study.18 

2.1.1. Defining the Study Problem.18 

2.1.2. Justifying the Study.19 

2.1.3. Identifying a Research Team To Plan and Implement the Study.20 

2.2. Ensuring Scientific Validity of the Research Study.20 

2.2.1. Study Design.20 

2.2.2. Feasibility.21 

2.2.3. Sample Size Determination.22 

2.2.4. Representativeness of the Sample.22 

2.2.5. Information Collection Rule.23 

2.2.6. Quality Assurance Project Plan.24 

2.2.7. The Study Design Document.24 

2.3. Ethical Issues in Ensuring Fair Subject Selection.24 

2.4. Ensuring a Favorable Risk-Benefit Ratio.25 

2.4.1. Designing in Benefits for the Participants.25 

2.4.2. Assessing Benefits and Risks of Study Participation.25 

2.5. Independent Scientific and Ethical Review.26 

2.5.1. Scientific Peer Review.27 

2.5.2. Conflicts of Interest.27 

2.5.3. Develop the Human Subjects Protocol for Institutional Review Board Review.28 

2.5.4. Ethical Review.29 

2.5.5. Internal U.S. EPA Review of Scientific and Ethical Issues.29 

2.6. Informed Consent.29 

2.7. Ensuring That Participant Behaviors Are Not Changed Adversely Because of 

Being in the Study .30 

2.8. Criteria and Standards for Monitoring Scientific and Ethical Issues.30 

3. Ensuring Protection of Vulnerable Groups.35 

3.1. Identification of Vulnerable Groups.35 

viii 









































3.2. Justification for Involving Vulnerable Persons in Observational Research.36 

3.3. Minimal Risk and Vulnerable Groups...37 

3.4. Research Involving Children.37 

3.5. Women as Research Subjects.38 

3.6. Other Potentially Vulnerable Groups.39 

4. Privacy, Confidentiality, and Other Concerns Related to Observational 

Human Exposure Studies.41 

4.1. Privacy Issues.41 

4.2. Confidentiality.42 

4.2.1. Confidentiality of Infonnation.43 

4.2.2. Confidentiality of Participation.44 

4.3. Collateral Observations.44 

4.3.1. Potential Nonstudy Hazards in the Residence.44 

4.3.2. Collateral Observations with Mandated Reporting Requirements.45 

4.3.3. Hazard Communication.45 

4.3.4. Planning and Staff Training.46 

4.4. Third-Party Issues.46 

4.4.1. Determining Whether a Third Party Is a Human Subject.47 

4.4.2. Informing Third Parties of Research Activities.47 

4.4.3. Research Results and Third Parties.47 

4.5. Data and Safety Monitoring and Oversight.48 

5. Creating an Appropriate Relationship Between the Participant and Researcher.51 

5.1. Informed Consent.52 

5.1.1. Information.52 

5.1.2. Comprehension.54 

5.1.3. Voluntary Participation.55 

5.2. Payments to Research Participants.56 

5.2.1. Types and Amounts of Payments Offered in Research Studies.56 

5.2.2. Regulations and Guidance Regarding Payment to Research Participants.58 

5.2.3. Payments When Children or Other Vulnerable Populations Are Involved.59 

5.2.4. Payments in Observational Human Exposure Studies.61 

5.3. Research Rights and Grievance Procedures.61 

5.3.1. Ombudsman.61 

5.3.2. Community Advisory Board.62 

5.4. Creating a Supportive Environment for Research and Interaction.62 

5.5. Recruitment Strategies.!.62 

5.6. Retention Strategies.63 

5.7. Ensuring Recruitment or Retention Methods Will Not Lead to Unacceptable Risk.64 

6. Building and Maintaining Appropriate Community and Stakeholder Relationships.67 

6.1. Approaches to Community Involvement.68 

6.2. Issues in Community Involvement.71 

6.2.1. Defining “Community”.71 

6.2.2. Identifying Who Represents the Community.71 

6.2.3. Building Relationships and Trust.72 

6.2.4. Importance of Language and Communications with the Community.73 

6.2.5. Recognizing and Addressing Cultural Differences.73 

6.2.6. Honesty, Power Relationships, and Partnerships..74 

6.2.7. Building a Lasting Infrastructure.74 

6.3. Community Involvement in Observational Human Exposure Studies.75 

6.4. Identifying and Interacting with Other Stakeholders.75 


IX 



















































7. Designing and Implementing Strategies for Effective Communication.81 

7.1 Communication Strategy and Implementation Plan.81 

7.2 Individuals and Groups Involved in the Communications.82 

7.3 Communications Timetables—When To Communicate.83 

7.4 Communicating at Different Levels.85 

7.5 Communications Materials.85 

7.6 Informing the Study Participants and Communities.87 

7.7 Reporting Study Results to the Participant and Community.87 

7.8 Reporting Unanticipated Results or Observations.90 

7.9 Anticipating and Responding to Criticism.91 

7.10 Responding to the Media, Public Inquiries, and Other Stakeholders.92 

Appendix A: Additional Discussion of Observational and Exposure Terminology and 

Examples of Previous NERL Observational Human Exposure Studies. 95 

Appendix B: The Process for Development of This Document: Description of the 
Expert Panel Workshop, the External Peer Review by the 

Human Studies Review Board, and Public Comment.107 

Appendix C: Recommended Content of a Human Subjects Protocol.Ill 

Appendix D: Recommendations for Enhancing Public Trust.113 

Appendix E: List of Acronyms and Abbreviations.1 15 

Appendix F: Glossary.117 


x 



















Executive Summary 


Scientists at the U.S. Environmental Protection 
Agency’s (EPA's) National Exposure Research 
Laboratory (NERL) have conducted observational 
human exposure studies for several decades to 
understand how people come into contact with 
chemicals and other stressors in their everyday lives, 
through the air they breathe, the food and liquids they 
consume, and the things they touch. These studies are 
performed to determine what chemicals people are 
exposed to, the concentrations of the chemicals, the most 
important sources contributing to people’s exposures, 
the routes and pathways of exposure, and the factors that 
have the biggest impact on exposure. The studies help 
explain when, where, why, how, and how often people 
are exposed to chemicals and other stressors (e.g., 
allergens, viruses, mold, radiation, noise) in their 
everyday environments as they go about their daily 
activities. Information from these studies helps EPA 
improve the understanding of people’s exposures to 
chemicals and other stressors and, ultimately, supports 
EPA’s efforts to protect public health. 

NERL scientists and managers take the protection of 
human subjects very seriously. Because observational 
human exposure studies involve people as research 
participants, NERL researchers must act to ensure the 
protection of the human subjects throughout the study. 
Such studies are often complex, and the specific actions 
will vary depending on the objectives of the study, the 
details of the study design and human subjects research 
protocol, and the details about the participants and the 
communities in which they live. To ensure that the 
actions of NERL researchers will properly respect, 
safeguard, and protect the rights and welfare of the 
participants in their research, NERL scientists need to be 
knowledgeable about the scientific and ethical issues 
that may arise as they plan and conduct their research, 
and they also need to be diligent in the application of the 
most up-to-date and sound scientific approaches and of 
the highest ethical standards to their research. 

This document, therefore, was prepared by NERL 
scientists as a resource and reference for EPA’s NERL 


scientists as they develop and implement observational 
human exposure studies. The authors recognize that this 
document also may prove to be useful to others involved 
in exposure science research, but that this document 
does not meet the definition of an official Agency 
“guidance document” (it does not set forth “a policy on a 
statutory, regulatory or technical issue or an 
interpretation of a statutory or regulatory issue”) and 
should not be used for that purpose. 

As EPA employees, NERL scientists face both 
regulatory> and moral and ethical obligations to ensure 
the protection of the human subjects participating in 
their observational research. The regulatory 
requirements are set forth in EPA’s human subjects 
regulations (40 CFR 26). The moral obligations derive 
from the ethical principles of biomedical ethics. NERL 
scientists and managers are resolved to meet both the 
“letter” of the law as set forth in the regulations and also 
the “spirit” that derives from the most up-to-date 
thinking and consensus on these sensitive issues. 

This document provides information on regulatory 
requirements and ethical issues to consider when 
performing human subjects research. Knowledge about 
these requirements and issues will help NERL scientists 
meet their goal of conducting observational human 
exposure studies based on the most up-to-date and sound 
science and the highest ethical scientific standards. 

The ethical and moral issues associated with human 
subjects research has long been the subject of a great 
deal of thought and discussion, both in the United States 
and abroad. Issues in biomedical ethics continue to be 
discussed and debated in today’s headlines. Spurred by 
the atrocities of World War II concentration camps and 
by the disclosure of unethical treatment of 
undereducated African-American men and other 
vulnerable groups by medical staff in the United States, 
the U.S. and world communities were prompted to 
establish ethical principles for medical and scientific 
experiments that involve people as participants. In the 
United States, the Belmont Report (U.S. DHEW, 1979) 
is the foundational document in the development of the 


1 


ethics of human subjects research. Tins report lays out 
the fundamental ethical principles behind research that 
involves humans as research subjects. These three basic 
principles, (1) respect for persons. (2) beneficence, and 
(3) justice, have become the cornerstones for regulations 
involving human subjects. Ethicists have expanded on 
those principles since 1979. translating them into ethical 
requirements that any human subjects research must be 
both ethically acceptable and scientifically sound. 1 
EPA's Science Advisors Board has affirmed. "Bad 
science is always unethical" (U S. EPA. 2000). 

In an effort to ensure that NERL's observational 
human exposure studies are founded on the ethical 
principles of respect for persons, beneficence and 
nonmaleficence, and justice and adhering to the principle 
that bad science is always unethical, scientists and 
managers from NERL have assembled this document as 
a resource and reference for NERL exposure scientists. 
These same scientists and managers have sought expert 
advice, including input from an expert panel workshop; 
review and comment on the external review draft of the 
document by the Human Studies Review Board (HSRB). 
a Federal advisory committee; public comment on the 
external review draft of the document; and public input 
about the state of the science for scientific and ethical 
approaches for design and implementation of 
observational human exposure studies. 

A number of references, both from the bioethics 
literature and from U.S. regulations, have proven useful 
to the authors as they have developed this document. 
Those references are listed in Table 1-4. which is 
replicated below. 

The authors also have relied extensively on the 
advice of an expert panel that convened in November 
2006 to provide advice and guidance about the structure 
and content of this document. The Expert Panel 
consisted of 11 nationally recognized authorities from 
diverse fields — exposure science, environmental health, 
bioethics, epidemiology, community-based research, 
law, research in minority communities, public health, 
toxicology, pediatrics, and children's environmental 
health. 

The Expert Panel Workshop resulted in suggestions 
for both the structure and the content of this document 
(ERG. 2007). Following the advice of the Expert Panel, 
this document is organized in seven sections. 


See. for example, the writings of Beauchamp and Childress in Principles of 
Biomedical Ethics (Beauchamp and Childress, 2001) and the discussion of 
"What Makes Clinical Research Ethical?” by Emanuel. Wendler. and Grady 
(Emanuel et at. 2000). 


Section 1 Introduction; The background tor 
observational human exposure studies, the scope ot 
this document, and the important scientific and ethical 
issues that are critical to human subjects and 
observational research 

Section 2. Elements to be considered in study 
conceptualization: Incorporating ethical concerns into 
the scientific effort from the onset and integrating 
them throughout all phases of study planning and 
implementation. As shown in the text box below, the 
planning process involves the initial identification ot 
the research question and justification of the research 
effort during the problem conceptualization phase. If 
human subjects research is justified for the study, the 
scientific and ethical approaches are described in the 
study design and the human subjects research 
protocol. The basic elements that should be included 
in the study design and in the human subjects research 
protocol are described, and researchers are advised to 
consider alternative and innovative study designs that 
maximize the benefits to the study participants and 
their community. Information is provided on both 
scientific peer review and ethical review, and the 
integration of the two. Mandated procedures for 
review by external peers, by Institutional Review 
Boards (IRBs), and by the EPA Human Subjects 
Research Review Official (HSRRO) are detailed. 


Problem 

Conceptualization 


Define & Justify 
the Study 


i 


Planning 

& 

Scoping 


( - 

Develop Study 
Design 


1 


Develop Human 
Subjects Protocol 


4 


l 


Independent 

Review 


Agency 

HSRRO 

Review 


Peer Review 


IRB Review 

Scientific & Ethical 


Ethical & Scientific 

Review 


Review 



Implement 

Study 

& 

Monitor 

Progress 


Criteria 
Continue Study 


Terminate Study 


Stages in the Development of a NERL 
Observational Human Exposure Study 


2 































Table 1-4. Important References in Developing This Document: 

Some Recent Developments in Defining the Ethics of Conducting Research Involving Human Participants 

Year 

Event/Report 

Description 

1979 

The Belmont Report: Ethical 
Principles and Guidelines for 
the Protection of Human 
Subjects of Research (U.S. 
DHEW, 1979) 

The Belmont Report attempts to summarize the basic ethical principles identified by the legislatively 
created National Commission for the Protection of Human Subjects of Biomedical and Behavioral 
Research. It is a statement of basic ethical principles and guidelines that should assist in resolving 
the ethical problems that surround the conduct of research with human subjects. The three basic 
ethical principles are (1) respect for persons, (2) beneficence, and (3) justice. 

1991 

The Common Rule 

40 CFR 26, Subpart A 

The Common Rule is a short name for “The Federal Policy for the Protection of Human Subjects" 
and was adopted by more than a dozen Federal departments or agencies in 1991. Each agency 
incorporated the policy into its own Code of Federal Regulations (CFR), with EPA adapting it in Title 

40 CFR Part 26, Subpart A. 

1993 

The Institutional Review 

Board Guidebook (U.S. HHS, 
1993) 

The document is intended as a resource and a reference document for IRB members, researchers, 
and institutional administrators. It is not designed to tell IRBs whether or not specific protocols should 
be approved: rather, the Guidebook points out issues to which IRBs should pay attention and 
presents, wherever possible, areas where ethicists have arrived at a consensus on the ethical 
acceptability of a particular activity or method. 

2000 

What Makes Clinical 

Research Ethical? (Emanuel 
et al„ 2000) 

This journal article lays out seven areas of concern that need to be addressed if clinical research is 
deemed to be ethically acceptable: (1) social or scientific value, (2) scientific validity, (3) fair subject 
selection, (4) favorable risk-benefit ratio, (5) independent review, (6) informed consent, and 
(7) respect for potential and enrolled subjects. 

2001 

Principles of Biomedical 
Ethics:(Fifth Edition 
(Beauchamp and Childress, 
2001) 

A classic text in biomedical ethics. Core chapters discuss respect for autonomy, nonmaleficence, 
beneficence, and justice. The chapter on professional-patient relationships discusses issues 
important to privacy, confidentiality, and protection of subjects. The fifth edition is an update that 
reflects developments in philosophical analysis, as well as developments in science and medicine. 

2002 

International Ethical 

Guidelines for Biomedical 
Research Involving Human 
Subjects (CIOMS, 2002) 

Developed by the Council for International Organizations of Medical Sciences particularly for use in 
developing countries, the guidelines relate mainly to ethical justification and scientific validity of 
research; ethical review; informed consent; vulnerability of individuals, groups, communities, and 
populations; women as research subjects; equity regarding burdens and benefits; choice of control in 
clinical trials; confidentiality; compensation for injury; strengthening of national or local capacity for 
ethical review; and obligations of sponsors to provide health care services. 

2003 

Protecting Participants and 
Facilitating Social and 
Behavioral Sciences 

Research (NRC, 2003) 

This NRC publication targets policymakers, research administrators, research sponsors, IRB 
members, and investigators. It examines three key ethical issues: (1) obtaining informed, voluntary 
consent from prospective participants; (2) guaranteeing the confidentiality of information collected 
from participants, which is a particularly challenging problem in social sciences research; and 
(3) using appropriate review procedures for minimal-risk research. 

2005 

Ethical Considerations for 
Research on Housing- 
Related Health Hazards 
Involving Children, (NRC & 
IOM, 2005) 

This National Research Council and Institute of Medicine report reviews the challenges and ethical 
issues in conducting housing-related health hazards research in the wake of the Maryland Court of 
Appeals ruling in the case of Grimes v. Kennedy Krieger Institute that has led to substantial 
controversy and confusion. The ruling highlighted a range of potential ethical concerns, such as 
issues involving adequacy of informed consent, parents' perception of risk, duties of researchers to 
child subjects and their parents, the role of IRBs, and the authority of parents to provide permission 
for their children to participate in research. This report offers much needed recommendations and 
practical guidance for the ethical conduct of this type of research. 

2006 

EPA adds Additional Human 
Subjects Protections at 

40 CFR 26 

EPA added additional human subjects protections in the Code of Federal Regulations to govern its 
actions. Subparts B through D apply to research conducted or supported by EPA and are directly 
applicable to NERL and this document. Subpart B prohibits research involving intentional exposure 
of children, pregnant women (and their fetuses), or nursing women. Subparts C and D provide 
additional protections for observational research involving pregnant women and their fetuses 
(Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use 
of third-party human research data. 

2008 

International Ethical 

Guidelines for 

Epidemiological Studies 
(CIOMS, 2008) 

This document builds on the CIOMS (2002) document (see above) and extends the discussion to 
address the special features of epidemiological studies. 


3 

















Section 3. Ensuring protection of vulnerable groups: 
Protections afforded by EPA’s human subjects rules 
and the ethical concerns of involving such groups in 
observational research. Special requirements for the 
protection of potentially vulnerable groups, including 
children, prisoners, pregnant women, handicapped 
persons, mentally disabled persons, and economically 
or educationally disadvantaged persons, throughout 
the planning and implementation process are 
described. 

Section 4. Addressing privacy and other concerns 
related to observational human exposure studies: 
Ethical issues and regulatory requirements concerning 
privacy, including third-party involvement and 
observations of nonstudy hazards. Unlike clinical 
research that is conducted in an institutional setting, 
observational human exposure studies take place in 
the participants’ “personal” environments as they go 
about their everyday lives, presenting an even greater 
challenge in meeting the ethical obligation to respect 
the privacy of the participants. 

Section 5. Creating an appropriate relationship between 
participant and investigator: Issues surrounding 
recruitment, informed consent, payment, and the 
researcher’s need to support the welfare of the 
participants. An appropriate relationship built on 
openness and trust requires strong and effective 
bidirectional communication. Infonned consent 
ensures that the participant understands the range of 
risks associated with participation and the voluntary 
nature of participation, and provides essential 
protections to the participant. Recent observations by 
various national and international review committees 
on the appropriate level of payment to research 
participants are presented. This is a complex ethical 
issue, balancing the issue of fairness against the 
possibility of undue influence and the loss of free 
consent. Other topics include participant recruitment, 
retention strategies, research rights, and grievance 
procedures. 

Section 6. Building and maintaining appropriate 
community and stakeholder relationships: Involving 
the community in the research effort to improve the 
research both scientifically and ethically. Various 
approaches are discussed related to issues such as 
defining the community, identifying who represents 
the community, recognizing and addressing cultural 
differences, and the importance of language, power 
relationships, and partnerships. 

Section 7. Designing and implementing strategies for 
effective communication: Ongoing, interactive 


dialogue among researchers, participants, the 
community, stakeholders, and the public to establish 
effective communications and to foster a relationship 
of trust. To facilitate information dissemination to 
participants, communities, and stakeholders, this 
section of the document describes communication 
strategies, implementation plans, communication 
groups, timetables, communication materials, and 
other tools available to researchers. 

This document does not and, indeed, could not 
provide solutions to all scientific and ethical issues that 
may arise as observational human exposure studies are 
undertaken. No document could identify and address all 
potential issues in advance, nor is it possible to develop 
a comprehensive checklist for all such studies. Rather, 
this document attempts to present and discuss the types 
of ethical and scientific issues that will need to be 
considered and addressed as NERL researchers plan and 
implement observational human exposure studies. The 
researchers will need to work with others — the study 
team, IRB members, EPA’s HSRRO, the participants 
and their community, and other stakeholders — to 
identify and address all of the relevant issues for any 
particular study. The authors are confident that this 
document will be helpful to NERL scientists in their 
endeavors to assure that all of NERL’s observational 
human exposure studies will respect, safeguard, and 
protect the participants in that research. 

References 

Beauchamp TL, Childress, JF (2001). Principles of 
Biomedical Ethics: Fifth Edition. New York, NY: Oxford 
University Press. 

CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I 
Environmental Protection Agency Part 26 Protection of 
Human Subjects. U.S. Code of Federal Regulations. 
Available: 

http://www.access.gpo.gov/nara/cfr/waisidx 06/40cfr26 06. 

html [accessed 12 June 2007], 

CIOMS (The Council for International Organizations of 
Medical Sciences) (2008). International Ethical Guidelines 
for Epidemiological Studies. World Health Organization. 
Geneva, Switzerland. Available: 
http://www.cioms.ch/080221 feb 2008.pdf [accessed 25 
April 2008]. 

CIOMS (The Council for International Organizations of 
Medical Sciences) (2002). International Ethical Guidelines 
for Biomedical Research Involving Human Subjects. World 
Health Organization. Geneva, Switzerland. Available: 


4 





http://www.cioms.ch/frame guidelines nov 2002.htm 

[accessed 12 June 2007], 

Emanuel EJ, Wendler D, Grady C (2000). What Makes 
Clinical Research Ethical? JAMA 20:2701-2711. 

ERG (Eastern Research Group) (2007). Report on the 
Workshop to Discuss State-of-the-Science Approaches for 
Observational Exposure Measurement Studies. Held in 
Durham, North Carolina on November 28-29, 2006. Final 
Report: January 25, 2007. (PB2007-108905). 

NRC (National Research Council) (2003) Protecting 
Participants and Facilitating Social and Behavioral 
Sciences Research. Washington, DC: The National 
Academies Press. Available: 
http://books.nap.edu/catalog.php7record id= 10638 

[accessed 12 June 2007], 

NRC & IOM (National Research Council and Institute of 
Medicine) (2005). Ethical Considerations for Research on 
Housing-Related Health Hazards Involving Children. 
Washington, DC: The National Academies Press. Available: 
http://books.nap.edu/catalog.php?record_id= 11450 

[accessed 12 June 2007], 


U.S. DHEW (U.S. Department of Health, Education, and 
Welfare) (1979) The Belmont Report: Ethical Principles 
and Guidelines for the Protection of Human Subjects of 
Research. National Commission for the Protection of 
Human Subjects of Biomedical and Behavioral Research. 
Available: http://ohsr.od.nih.gov/guidelines/belmont.html 
[accessed 12 June 2007], 

U.S. EPA (U.S. Environmental Protection Agency) (2000) 
Comments on the Use of Data from the Testing of Human 
Subjects: A Report by the Science Advisory Board and the 
FIFRA Scientific Advisory’ Panel. United States 
Environmental Protection Agency, Science Advisory Board, 
EPA-SAB-EC-00-017. Available: 

http://yosemite.epa.gov/sab/SABPRODUCT.NSF/E3AEOF3 

0D7430436852571 A7005325E8/SFile/ec0017.pdf [accessed 
12 June 2007], 

U.S. HHS (U.S. Department of Health and Human Services) 
(1993). Protecting Human Research Subjects: Institutional 
Review Board Guidebook. Office for Human Research 
Protections. Available: 

http://www.hhs.gov/ohrp/irb/irb guidebook.htm [accessed 
12 June 2007], 


5 


















































SECTION 1 


Introduction, Purpose, and Scope 


Observational human exposure studies are an 
important research tool for understanding people’s 
contact with pollutants and other stressors in the 
environment, that is, their exposure. 2 3 Such studies allow 
researchers to collect information about people’s 
exposures to chemicals and other stressors under real- 
world conditions during their normal day-to-day 
activities. Exposures occur through the air we breathe, 
the food we eat, the water and beverages we drink, and 
the surfaces that we touch as we go about our daily 
routines. To understand and characterize people’s 
exposures to chemicals, two things have to be known: 
(1) the concentrations of the chemicals in the 
environment that people inhale, ingest, or touch; and (2) 
the human activities that bring people into contact with 
the media containing the chemicals. 2 This document 
addresses issues associated with observational human 
exposure studies that are conducted by the National 
Exposure Research Laboratory (NERL) of the U.S. 
Environmental Protection Agency (EPA) in an effort to 
understand and characterize the exposures that people 
encounter as they go about their daily lives. 

Because observational human exposure studies 
involve human participants, they are complex in their 
design and implementation. As in all research involving 
human participants, observational human exposure 
studies carry both regulatory obligations for the 
protection of human subjects (40 CFR 26) and ethical 
obligations to the study participants: namely, to respect 


2 Exposure , as it is used throughout this document, is a technical term that is 
defined as the "contact of a chemical, physical, or biological agent with the 
outer boundary of an organism [e.g., a person]. Exposure is quantified as the 
concentration of the agent in the medium in contact integrated over the time 
duration of that contact.” (The definition is taken from Guidelines for 
Exposure Assessment [EPA/600/Z-92/001, May 1992]). See the Glossary for 
more information and the definition of additional terms. 

3 The term “chemical” is used in this document as a surrogate term for all 
stressors, including chemical, physical, or biological agents. 


their autonomy, to not inflict harm (nonmaleficence), to 
avoid harm and to maximize their benefits (beneficence), 
and to treat all participants fairly (justice) (See, for 
example. Principles of Biomedical Ethics , Beauchamp 
and Childress, 2001). Ethical obligations have to be 
carefully considered as they relate to the scientific 
elements of these studies. Therefore, it is important that 
researchers recognize and understand these obligations 
and use the most up-to-date scientific and ethical 
approaches in the design and implementation of 
observational human exposure studies. 

1.1 Observational Human Exposure Studies 

As we are using the term in this document, 
“observational human exposure studies” are studies that 
involve the collection of environmental samples, data, 
and information from study participants in their 
everyday environments as they go about their normal 
activities. These are studies where the NERL researchers 
do not intentionally try to control the study variables or 
outcomes, but instead merely observe both the variables 
and the outcomes. They involve neither the deliberate 
exposure of participants nor the control of environmental 
conditions in a way that impacts the participants’ 
naturally occurring exposures. This scientifically based 
definition needs to be distinguished at the outset from 
the broader regulatory term “observational” so that the 
scope and limits of this document are clear. EPA 
Regulation 40 CFR 26 (Protection of Human Subjects) 
at Subpart B, first, defines research involving intentional 
exposure of a human subject as “a study of a substance 
in which the exposure to the substance experienced by a 
human subject participating in the study would not have 
occurred but for the human subject’s participation in the 
study” [40 CFR 26.202(a)]. It then goes on at Subpart C 
to define observational research as “any human research 
that does not meet the definition of research involving 
intentional exposure of a human subject (40 CFR 


7 






26.302). By defining “observational” so broadly, a 
regulatory category is created that encompasses a range 
of study types whose only common feature is that they 
do not entail “intentional exposure” as defined in the 
regulations. Moreover, some of these “observational” 
study types do not involve the study of exposures at all 
but rather “observe” other sorts of phenomena. The 
observational human exposure studies with which we are 
concerned here, on the other hand, are exposure studies, 
but they represent a narrower group of studies as defined 
scientifically at the beginning of this paragraph. 
Although they would generally be expected to fall within 
the regulatory category of “observational research”, they 
are not synonymous with it. (For a more thorough 
discussion of the scientific and regulatory meanings of 
observational and exposure , with examples, please see 
Appendix A.) 

Observational human exposure studies are 
performed for many different purposes. They have been 
used extensively in the fields of social behavioral, 
economic, biological, medical, epidemiological, and 
exposure research to collect information that relates one 
or more variables (e.g., exposure to a chemical) to its 
result (e.g., the concentration of an exposure biomarker 
in blood). There are many examples of observational 
human exposure studies that have been conducted over 
the past decade, and the reader is referred to the Journal 
of Exposure Science and Environmental Epidemiology 
and to Environmental Health Perspectives for examples 
of the objectives, designs, and results of these studies. 

NERL researchers have conducted and relied on 
observational human exposure studies for more than 
three decades. Examples of studies conducted or funded 
by NERL are listed in Appendix A, Table A-l. Common 
goals in those studies included those that follow. 

• Identity which chemicals or other stressors that people 
are exposed to during their normal activities in the 
environments that they occupy. 

• Measure the concentrations of the chemicals to which 
people are exposed. 

• Identify the most important routes and pathways of 
exposure. 

• Identify the factors that impact people’s exposures 
(i.e., determine the when, why, how, and how much 
that people are exposed to chemicals in the 
environment). 

These studies involve many different types of data 
collection efforts and typically include observations. 


measurements, and information on the following items. 

• Chemical concentrations in environmental media (air, 
water, soil, floor dust, and dust on surfaces) 

• Chemical concentrations in the diet (food and 
beverages). 

• Biomonitoring (measurements of biomarkers of 
exposure in urine, blood, and saliva) 

• Time, location, and activity information 

• Information on personal activities, product use, diet, 
occupation, and other factors that may impact 
exposure 

• Information on the characteristics of the environments 
that study participants occupy (homes, schools, 
offices, public access buildings, etc.) 

The information obtained in observational human 
exposure studies is used to better understand people’s 
contact with chemicals in the environment and to 
improve exposure assessments and risk assessments. 
This information is also essential for developing risk 
mitigation strategies and for developing educational 
materials and programs for reducing exposures and risks 
to chemicals or other stressors in the environment (see 
Table 1-1). 

1.2 Ethical Issues in Observational Human 
Exposure Studies 

By definition, observational human exposure studies 
involve human subjects. Whenever their research 
involves human subjects, EPA researchers are required 
to ensure the protection of the study participants by 
complying with the Agency’s human subjects rules as 
set forth in 40 CFR 26. 

The Common Rule (Subpart A of the rules) 
represents basic regulatory actions (common to more 
than a dozen Federal departments or agencies) that are 
intended to ensure the protection of all human subjects. 
The central requirements of the Common Rule are 
twofold: 

(1) that people who participate as subjects in covered 
research are selected equitably and give their fully 
informed, fully voluntary written consent; and 

(2) that proposed research be reviewed by an 
independent oversight group referred to as an 
institutional review board (IRB) and approved only if 
risks to subjects have been minimized, and risks are 
reasonable in relation to anticipated benefits, if any, to 
the subjects and to the importance of the knowledge that 
may realistically be expected to result. 


8 


Table 1 -1. Examples of the Impact of Observational Human Exposure Studies on Pollution Levels and Regulatory Actions 

Pollutant 

Observational Study Result 

Impact/Action/Result 

Particulate Matter (PM) 

Observational panel studies demonstrated 
the appropriateness of ambient measurement 
of fine particles as a surrogate for a 
population's longitudinal exposure to fine PM. 

Resolved questions in NAS review of PM science and provided a 
“generally consistent finding that ambient particle concentrations are 
a key determinant of the longitudinal variation in personal exposure.” 
(NRC, 2004). These results have been instrumental in support of the 
National Ambient Air Quality Standard for PM (U.S. EPA, 1999). 

Volatile Organic Compounds 
(VOCs) 

EPA’s Total Exposure Assessment 
Methodology (TEAM) studies found levels of 
about a dozen common organic pollutants to 
be 2- to 5-times higher inside homes than 
outside. Use of products containing organic 
chemicals may result in very high and 
persistent pollutant levels. 

EPA, States, and the Consumer Product Safety Commission worked 
together to influence manufacturers to voluntarily reduce emissions of 
toxic chemicals from consumer products, building materials, and 
furnishings, and to develop mitigation strategies and educational 
materials to teach people how to reduce their contact with chemicals 
indoors. As a result, contact with toxic chemicals indoors has been 
reduced (see www.cpsc.gov/CPSCPUB/PUBS/450.html). 

Formaldehyde 

Studies found elevated formaldehyde levels 
indoors and helped identify indoor sources. 

EPA worked with HUD, CPSC, and other agencies to limit 
formaldehyde in building or consumer products and to educate the 
public on how to reduce exposures (see www. 
epa.gov/iaq/formalde.html). 


EPA has adopted additional protections for children 
and pregnant or nursing mothers in Subparts B through 
D. These sections apply to all research either conducted 
or funded by EPA and are, therefore, directly applicable 
to NERL’s observational human exposure studies. 4 5 
Subpart B prohibits EPA from conducting or supporting 
research that involves intentional exposure of “a 
pregnant woman (and, thereby, her fetus), a nursing 
woman, or a child.” NERL researchers conducting (or 
funding) observational human exposure studies must 
comply with all of these regulatory requirements, 
including seeking review and approval by an IRB and by 
the Agency’s Human Subjects Research Review Official 
(HSRRO) before beginning any human subjects 
research. EPA’s human subjects rules also define a 
variety of fundamental terms—from “human subject” to 
“research” to “intentional exposure” to “observational 
research.” Understanding these regulatory definitions is 
vital for NERL researchers to comply with the 
regulatory requirements.' 

To more effectively ensure the protection of human 
subjects, NERL scientists and managers need to 
understand the ethical principles and issues that 
prompted the development of the regulatory 
requirements in the first place and to be knowledgeable 


4 Subparts K, L, M, O. P, and Q of 40 CFR 26 set basic ethical requirements 
that have to be met if human subjects data from a person or group external to 
EPA and not funded by EPA (a third party) are to be used by EPA in specified 
rulemaking actions. These subparts do not apply to NERL researchers and 
will not be discussed further in this document. 

5 The Glossary (Appendix F) lists definitions for a number of important terms; 
definitions that come from the regulatory language are identified with their 
specific CFR citation. 


about the most recent thinking and guidance on 
protection of human subjects. 

The Belmont Report (U.S. DHEW, 1979) is a 
foundational document in the development of the ethics 
of human subjects research in the Efnited States. Because 
of the adverse publicity and political embarrassment 
arising from the unethical treatment of African- 
American men in the Tuskegee Syphilis Study, Congress 
passed the National Research Act of 1974, which called 
on the Department of Health, Education, and Welfare 
(DHEW) to codify its rules on human subjects research 
and established the National Commission for the 
Protection of Human Subjects of Biomedical and 
Behavioral Research. The commission was charged with 
identifying the basic ethical principles that should 
underlie human subjects research. The commission 
published the Belmont Report in 1979. This report 
established three basic principles: (1) respect for 
persons; (2) beneficence; and (3) justice, which have 
become the cornerstones for regulations involving 
human subjects (see Table 1-2). 

In 1981, the Department of Health and Human 
Services (HHS) issued regulations based on the Belmont 
Report. Ten years later, the core HHS regulations 
(Subpart A) were adopted by almost all of the Federal 
departments and agencies that conducted or sponsored 
human subjects research as the “Common Rule.” 

Since 1991, ethical thought and regulatory processes 
for the protection of human subjects have continued to 
evolve and grow. For example, many ethicists expand 
the elements contained in the principle of beneficence 
from the Belmont Report into two principles: 
(1) beneficence, meaning to prevent or remove harm and 


9 











to maximize the possible benefits; and 
(2) nonmaleficence, meaning not to inflict harm 
(Beauchamp and Childress, 2001). 


Table 1-2. The Belmont Report— 

Principles and Recommendations 

Ethical Principle 

Regulatory Manifestation 

Respect for Persons 

• Individuals should be 
treated as autonomous 
agents. 

• Persons with diminished 
autonomy are entitled to 
protection. 

Informed Consent 

• Subjects must be given the 
opportunity to choose what will or 
will not happen to them 

• The consent process must include 

(1) information, 

(2) comprehension, and 

(3) voluntariness 

Beneficence 

• Human subjects should 
not be harmed. 

• Research should 
maximize possible 
benefits and minimize 
possible harms. 

Assessment of Risks and 

Benefits 

• The nature and scope of risks and 
benefits must be assessed in a 
systematic manner. 

Justice 

• The benefits and risks of 
research must be 
distributed fairly. 

Selection of Subjects 

• There must be fair procedures and 
outcomes in the selection of 
research subjects. 


In 2000, Emanuel, Wendler, and Grady considered 
the ethical principles involved in clinical research and 
proposed seven ethical requirements to be addressed in 
research with humans (Emanuel et al., 2000). Their 
published article specifically addressed clinical research, 
but the issues are similar for observational human 
exposure studies. Their ethical requirements are 
summarized and briefly explained in Table 1-3. The 
requirements are a logical extension of the ethical 
principles enunciated in the Belmont Report and 
manifest themselves in additional requirements for 
social or scientific value; for processes to ensure the 
scientific integrity of the research; and for independent 
review of the design, the subject population, and the 
risk-benefit ratio. The principle of respect for subjects 
also includes additional emphasis on the welfare of the 
subjects. 

More recently, there has been increased scrutiny and 
discussions of the ethics of research involving human 
participants, 6 and a number of respected institutions have 


6 The term "human participants" often is used in this document. It denotes the 
importance of the study participant being actively engaged in a partnership 
with the researchers to address the objectives and goals of the study. The term 
should be considered to be synonymous with the term “human subject” as 
used in the Common Rule and in documents used to describe regulatory 
requirements for studies involving human subjects. 


addressed many important scientific and ethical issues 
on this topic, including the National Research Council 
(NRC) in its report. Protecting Participants and 
Facilitating Social and Behavioral Sciences Research 
(NRC, 2003), a joint NRC and Institute of Medicine 
(NRC & IOM, 2005) committee in the report on Ethical 
Considerations for Research on Housing-Related Health 
Hazards Involving Children ; the Council for 
International Organizations of Medical Sciences 
(CIOMS) under the World Health Organization in its 
International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (CIOMS, 2002) and 
in the International Ethical Guidelines for 
Epidemiological Studies (CIOMS, 2008); and the 
National Ethics Advisory Committee of New Zealand in 
the Ethical Guidelines for Observational Studies: 
Obser\>ational Research, Audits and Related Activities 
(NEAC, 2006). 


Table 1-3. Seven Ethical Requirements for 

Clinical Research 

From Emanuel, Wendler, and Grady (2000) 

Requirement 

Explanation 

Social or 
scientific value 

Evaluation of a treatment, intervention, or theory 
that will improve health and well-being or 
increase knowledge 

Scientific 

validity 

Use of accepted scientific principles and 
methods, including statistical techniques, to 
produce reliable and valid data 

Fair subject 
selection 

Selection of subjects so that stigmatized and 
vulnerable individuals are not targeted for risky 
research, and the rich and socially powerful are 
not favored for potentially beneficial research 

Favorable risk- 
benefit ratio 

Minimization of risks; enhancement of potential 
benefits and risks to the subject are 
proportionate to the benefits to the subject and to 
society 

Independent 

review 

Review of the design of the research trial, its 
proposed subject population, and risk-benefit 
ratio by individuals unaffiliated with the research 

Informed 

consent 

Provision of information to subjects about the 
purpose of the research and its procedures, 
potential risks, benefits, and alternatives, so that 
the individual understands this information and 
can make a voluntary decision whether to enroll 
and continue to participate 

Respect for 
potential and 
enrolled 
subjects 

Respect for subjects by 

• permitting withdrawal from the research, 

• protecting privacy through confidentiality, 

• informing subjects of newly discovered risks 
or benefits, 

• informing subjects of results of the research, 
and 

• maintaining welfare of subjects. 


10 



















Collectively, these documents have reaffirmed the 
basic ethical principles asserted in the Belmont Report 
and have attempted, in some cases, to expand scientific 
and ethical reasoning and understanding to define 
approaches for dealing with additional elements of 
human subjects research. These additional elements, 
which often have been identified because of specific 
incidents or case studies, include issues such as those 
described below. 

• Payment to participants—How much is adequate and 
fair, without being an undue inducement? 

• Non-study hazards—What is the researcher’s 

responsibility to identify hazards in the home that are 
not part of the study? 

• Third-party issues—Are there people other than the 
participant who may be impacted during the study and 
by the study results? If so, what needs to be done to 
protect their interests and to respect them as persons? 

• Community involvement—How should the 

community be involved in the design and 
implementation of studies? 

These documents, together with EPA’s regulatory 
requirements for the protection of human subjects, serve 
as important references for the subsequent sections of 
this document (see Table 1-4). 

1.3 Purpose of This Document 

This document is meant to serve as a resource of 
current scientific and ethical information for NERL 
researchers as they develop and conduct observational 
human exposure studies. The increased scrutiny of 
research studies involving human participants makes it 
imperative that researchers ensure that their research 
protocols for protection of human subjects in 
observational human exposure studies incorporate the 
most up-to-date ethical approaches. Protocols for 
protecting study participants in research studies have 
been developed by experts in both academia and various 
Federal agencies and adopted by the research 
community because they ensure that observational 
research meets the highest ethical and scientific 
standards. However, because ethical and scientific 
approaches for human subjects research continue to be 
refined and evolve over time, there is a continuing need 
to evaluate the latest approaches and ensure that 
researchers are using state-of-the-science approaches in 
their design and implementation of such studies. 

The purpose of this document is to provide 
information that researchers in EPA’s Office of 
Research and Development’s NERL can use in the 
design and implementation of observational human 


exposure studies to ensure the protection of the human 
study participants. It is intended to be a resource tool for 
NERL’s exposure science researchers, but it is not 
intended to serve as a “guidelines” document or a “how¬ 
to” checklist. This document does not meet the Office of 
Management and Budget (OMB) definition for an 
official Agency “guidance document” (“Guidance 
document - an agency statement of general applicability 
and future effect, other than a regulatory action ... that 
sets forth a policy on a statutory, regulatory or technical 
issue or an interpretation of a statutory or regulatory 
issue” [U.S. OMB, 2007]). The authors, as researchers, 
perceived the need to provide this document for 
themselves, their co-workers, and their collaborators, but 
do not presume to speak for the whole of the Agency. 
The authors have tried to (1) identify major areas and 
elements of observational human exposure studies for 
which ethical issues need to be considered, (2) provide 
information on the state of the science for selected 
approaches for applying ethical principles to the conduct 
of these studies, and (3) provide sources of information 
that researchers can use in the design and 
implementation of these studies. 

The emphasis of this document is to identify and 
discuss ethical issues and approaches in observational 
human exposure studies. As the document title implies 
and as discussed in Section 2, scientific and ethical 
issues are intrinsically bound together in research 
involving human subjects. Therefore, it is essential that 
scientific and ethical issues be considered together, not 
separately. In this document, scientific issues and 
approaches are discussed as they relate to and impact 
ethical issues. However, it is beyond the scope of this 
document to present a comprehensive discussion of the 
scientific approaches for observational human exposure 
studies. To include a comprehensive discussion of 
scientific approaches in this document would reduce the 
utility of the document by increasing the complexity of 
the presentation and the length of the document. 

This document does not provide solutions to all 
scientific and ethical issues that may arise as such 
studies are undertaken. That is, it is not possible to 
identify or address all potential issues in advance or 
develop a comprehensive checklist for all such studies. 
Rather, this document attempts to present and discuss 
the types of issues that will need to be considered and 
addressed as NERL researchers plan and implement 
observational human exposure studies. The researchers 
will need to work with others—the study team, IRB 
members, EPA HSRRO, the participants and their 
community, and other stakeholders—to identify and 


11 




Table 1-4. Important References in Developing This Document: 

Some Recent Developments in Defining the Ethics of Conducting Research Involving Human Participants 

Year 

Event/Report 

Description 

1979 

The Belmont Report: Ethical 
Principles and Guidelines for 
the Protection of Human 
Subjects of Research (U.S. 
DHEW, 1979) 

The Belmont Report attempts to summarize the basic ethical principles identified by the legislatively 
created National Commission for the Protection of Human Subjects of Biomedical and Behavioral 
Research. It is a statement of basic ethical principles and guidelines that should assist in resolving 
the ethical problems that surround the conduct of research with human subjects. The three basic 
ethical principles are (1) respect for persons, (2) beneficence, and (3) justice. 

1991 

The Common Rule 

40 CFR 26, Subpart A 

The Common Rule is a short name for “The Federal Policy for the Protection of Human Subjects" 
and was adopted by more than a dozen Federal departments or agencies in 1991. Each agency 
incorporated the policy into its own Code of Federal Regulations (CFR), with EPA adapting it in Title 

40 CFR Part 26, Subpart A. 

1993 

The Institutional Review 

Board Guidebook (U.S. HHS, 
1993) 

The document is intended as a resource and a reference document for IRB members, researchers, 
and institutional administrators. It is not designed to tell IRBs whether or not specific protocols should 
be approved; rather, the Guidebook points out issues to which IRBs should pay attention and 
presents, wherever possible, areas where ethicists have arrived at a consensus on the ethical 
acceptability of a particular activity or method. 

2000 

What Makes Clinical 

Research Ethical? (Emanuel 
et al„ 2000) 

This journal article lays out seven areas of concern that need to be addressed if clinical research is 
deemed to be ethically acceptable: (1) social or scientific value, (2) scientific validity, (3) fair subject 
selection, (4) favorable risk-benefit ratio, (5) independent review, (6) informed consent, and 
(7) respect for potential and enrolled subjects. 

2001 

Principles of Biomedical 
Ethics:(Fifth Edition 
(Beauchamp and Childress, 
2001) 

A classic text in biomedical ethics. Core chapters discuss respect for autonomy, nonmaleficence, 
beneficence, and justice. The chapter on professional-patient relationships discusses issues 
important to privacy, confidentiality, and protection of subjects. The fifth edition is an update that 
reflects developments in philosophical analysis, as well as developments in science and medicine. 

2002 

International Ethical 

Guidelines for Biomedical 
Research Involving Human 
Subjects (CIOMS, 2002) 

Developed by the Council for International Organizations of Medical Sciences particularly for use in 
developing countries, the guidelines relate mainly to ethical justification and scientific validity of 
research; ethical review; informed consent; vulnerability of individuals, groups, communities, and 
populations; women as research subjects; equity regarding burdens and benefits; choice of control in 
clinical trials; confidentiality; compensation for injury; strengthening of national or local capacity for 
ethical review; and obligations of sponsors to provide health care services. 

2003 

Protecting Participants and 
Facilitating Social and 
Behavioral Sciences 

Research (NRC, 2003) 

This NRC publication targets policymakers, research administrators, research sponsors, IRB 
members, and investigators. It examines three key ethical issues: (1) obtaining informed, voluntary 
consent from prospective participants; (2) guaranteeing the confidentiality of information collected 
from participants, which is a particularly challenging problem in social sciences research; and 
(3) using appropriate review procedures for minimal-risk research. 

2005 

Ethical Considerations for 
Research on Housing- 
Related Health Hazards 
Involving Children, (NRC & 
IOM, 2005) 

This National Research Council and Institute of Medicine report reviews the challenges and ethical 
issues in conducting housing-related health hazards research in the wake of the Maryland Court of 
Appeals ruling in the case of Grimes v. Kennedy Krieger Institute that has led to substantial 
controversy and confusion. The ruling highlighted a range of potential ethical concerns, such as 
issues involving adequacy of informed consent, parents' perception of risk, duties of researchers to 
child subjects and their parents, the role of IRBs, and the authority of parents to provide permission 
for their children to participate in research. This report offers much needed recommendations and 
practical guidance for the ethical conduct of this type of research. 

2006 

EPA adds Additional Human 
Subjects Protections at 

40 CFR 26 

EPA added additional human subjects protections in the Code of Federal Regulations to govern its 
actions. Subparts B through D apply to research conducted or supported by EPA and are directly 
applicable to NERL and this document. Subpart B prohibits research involving intentional exposure 
of children, pregnant women (and their fetuses), or nursing women. Subparts C and D provide 
additional protections for observational research involving pregnant women and their fetuses 
(Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use 
of third-party human research data. 

2008 

International Ethical 

Guidelines for 

Epidemiological Studies 
(CIOMS, 2008) 

This document builds on the CIOMS (2002) document (see above) and extends the discussion to 
address the special features of epidemiological studies. 


12 

















address all of the relevant issues for their particular 
study to ensure that the specific elements of the study 
will safeguard and protect the human research subjects. 

In addition to being an information resource for 
NERL researchers, this document provides useful 
information for contractors and grantees funded by 
NERL to consider during the design and implementation 
of their exposure science research. Although not its 
intended audience, this document also may prove to be 
useful to other researchers, within and outside of EPA, 
who are involved in observational human exposure 
studies. 

1.4 Process for Developing the Document 

This document was written by exposure science 
researchers in EPA’s NERL, with substantial input from 
experts within and outside of the Agency. Information 
relevant to the process and the document has been 
routinely posted on the EPA Web site at 
http://www.epa.gov/nerl/sots . 

NERL staff began this work by hosting a series of 
stakeholder meetings in the summer of 2006 to seek 
input on the content and format of the document. In 
November 2006, NERL convened an expert panel to 
provide its advice and guidance about the scope and 
content of this document. The Expert Panel consisted of 
11 nationally recognized authorities in diverse fields: 
exposure science, environmental health, bioethics, 
epidemiology law, community-based research, research 
in minority communities, public health, toxicology, 
pediatrics, children’s environmental health, etc. Details 
about the Expert Panel and the workshop can be found in 
Appendix B. The summary report from the Expert Panel 
may be accessed online at 

http://www.epa.gov/nerl/sots/workshop-report.pdf . 

The structure and content of the current report 
follow the recommendations of the Expert Panel. 
Specifically, the Expert Panel recommended that this 
document should include the following six major topic 
areas: 

(1) elements to be considered in study 
conceptualization, 

(2) ensuring protection of vulnerable groups, 

(3) addressing privacy and other concerns related to 
observational human exposure studies, 

(4) creating an appropriate relationship between the 
participant and investigator, 

(5) building and maintaining appropriate community 
and stakeholder relationships, and 

(6) designing and implementing strategies for effective 
communication. 


These recommendations include pragmatic steps that 
NERL scientists can undertake during the development 
and implementation of observational human exposure 
studies. Note that each step may require consideration 
and application of multiple ethical and scientific 
principles, and the same ethical principle may be 
fundamental to several of the topic areas. As a result, the 
same ethical principle may be discussed in several 
sections throughout this document. 

Using the advice of the Expert Panel, an internal 
review draft of the document was written. Based on the 
comments from internal EPA reviewers, the internal 
review draft was revised, and an external review draft 
was prepared. The external review draft was submitted 
for peer review by EPA’s Human Subjects Review 
Board (HSRB), a Federal advisory committee consisting 
of a panel of experts chartered to review and advise the 
Agency on the scientific and ethical underpinnings of 
human subjects research efforts. The external review 
draft also was announced in the Federal Register and 
made available for public review and comment. The 
document subsequently was revised in response to 
comments from the HSRB and from the public in 
preparation for publication and release as an EPA report. 
EPA’s response to comments was posted to the draft 
report’s docket (EPA-HQ-ORD-2007-0972) at 
www.regulations.gov . 

1.5 Organization of the Document 

The document is organized along the lines that the 
Expert Panel recommended. It has seven sections, an 
introduction followed by a section addressing each of the 
major topic areas. The content of each section also is 
based on recommendations from the Expert Panel 
Workshop. Because the authors concluded that the 
discussion for each topic area needed to be complete in 
and of itself (i.e., capable of standing independently 
without having to reference other sections), there may be 
some issues or topics that are discussed in several 
sections. Appendixes include additional descriptions of 
NERL observational human exposure studies, details 
about the process for developing this document, a list of 
acronyms and abbreviations, a glossary, and other 
supplemental information. The main body of the 
document includes the following sections. 

• Introduction, Purpose, and Scope (Section 1) lays out 
the background for observational human exposure 
studies, the scope of the document, and some of the 
important scientific and ethical issues that are critical 
to human subjects and observational research. 


13 





• Study Conceptualization and Planning (Section 2) 
establishes that ethical concerns are to be incorporated 
in the scientific effort from the very beginning and 
includes ethical issues such as justifying the study 
because of its social and scientific merit and ensuring 
scientific validity and independent review. 

• Protection of Vulnerable Groups (Section 3) discusses 
some of the special protections afforded to vulnerable 
groups by EPA’s human subjects rules and the ethical 
issues of involving such groups in observational 
research. 

• Ensuring Privacy and Confidentiality (Section 4) lays 
out the ethical issues and the regulatory requirements, 
including observations of nonstudy hazards and the 
recently discussed issues of third-party involvement or 
concerns. 

• The Relationship Between the Participant and the 
Researcher (Section 5) builds on the ethical principles 
of respect for persons and beneficence to discuss the 
issues around recruitment, informed consent, 
payment, and the researcher’s need to support the 
welfare of the participants. 

• Community and Stakeholder Relationships (Section 6) 
begins with the principles of fairness, justice, and 
equity and of respect for persons to develop 
approaches to demonstrate respect for culture and to 
empower the participants’ community to endure, 
including the need to build trust in the community and 
with stakeholders through open and honest 
communications and legitimate power sharing. 

• Strategies for Effective Communication (Section 7) 
builds on the presumption of an ongoing, interactive 
dialogue and exchange of ideas between researchers 
and the participants, community, and stakeholders and 
focuses on steps that the researcher needs to take for 
effective communications. The section discusses 
communication strategies, implementation plans, 
communication tools, reporting of results, and 
approaches for effective communications, two-way 
communications between the researchers, participants, 
community, and other stakeholders. 

References 

Beauchamp TL, Childress, JF (2001). Principles of 
Biomedical Ethics: Fifth Edition. New York, NY: Oxford 
University Press. 

CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I 
Environmental Protection Agency Part 26 Protection of 
Human Subjects. U.S. Code of Federal Regulations. 
Available: http://www.access.gpo.gov/nara/cfr/waisidx 06/ 
40cfr26 06.html [accessed 12 June 2007]. 


CIOMS (The Council for International Organizations of 
Medical Sciences) (2008). International Ethical Guidelines 
for Epidemiological Studies. Geneva, Switzerland: CIOMS. 
Available: http://www.cioms.ch/080221 feb 2008.pdf 
[accessed 25 April 2008]. 

CIOMS (The Council for International Organizations of 
Medical Sciences) (2002). International Ethical Guidelines 
for Biomedical Research Involving Human Subjects. 
Geneva, Switzerland: CIOMS. Available: 
http://www.cioms.ch/frame guidelines nov 2002.htm 

[accessed 12 June 2007]. 

Emanuel EJ, Wendler D, Grady C (2000). What Makes 
Clinical Research Ethical? JAMA 283(20): 2701-2711. 

NEAC (National Ethics Advisory Committee) (2006). Ethical 
Guidelines for Observational Studies: Observational 
research audits and related activities. Wellington, New 
Zealand: Ministry of Health. Available: 
http://www.neac.health.govt.nz/moh.nsf/indexcm/neac- 

resources-publications-ethicalguidelines . 

NRC (National Research Council) (2004) Research Priorities 
for Airborne Particulate Matter: IV. Continuing Research 
Progress. Washington, DC: The National Academies Press. 
Available: 

http://books.nap.edu/openbook.php7record id= 10957 

[accessed 16 August 2007], 

NRC (National Research Council) (2003) Protecting 
Participants and Facilitating Social and Behavioral 
Sciences Research. Washington, DC: The National 
Academies Press. Available: 
http://books.nap.edu/catalog.php7record id^ 10638 

[accessed 12 June 2007]. 

NRC & 10M (National Research Council and Institute of 
Medicine) (2005). Ethical Considerations for Research on 
Housing-Related Health Hazards Involving Children. 
Washington, DC: The National Academies Press. Available: 
http://books.nap.edu/catalog.php7record id=l 1450 

[accessed 12 June 2007]. 

U.S. DHEW (U.S. Department of Health, Education, and 
Welfare) (1979) The Belmont Report: Ethical Principles 
and Guidelines for the Protection of Human Subjects of 
Research. National Commission for the Protection of 
Human Subjects of Biomedical and Behavioral Research. 
Available: http://ohsr.od.nih.gov/guidelines/belmont.html 
[accessed 12 June 2007]. 

U.S. EPA (U.S. Environmental Protection Agency) (1999). 

Air Quality Criteria for Particulate Matter. Environmental 
Protection Agency, National Center for Environmental 
Assessment, Office of Research and Development. 
EPA/600/P-99/002. 


14 












U.S. EPA (U.S. Environmental Protection Agency) (1992). 
Guidelines for Exposure Assessment. Environmental 
Protection Agency, Risk Assessment Forum. EPA/600/Z- 
92/001. Available: 

http://oaspub.epa.gov/eims/eimscomm.getfile7p download 

id=429103 [accessed 15 April 2008]. 

U.S. HHS (U.S. Department of Health and Human Services) 
(1993). Protecting Human Research Subjects: Institutional 
Review Board Guidebook. Office for Human Research 


Protections. Available: 

http://www.hhs.gov/ohrp/irb/irb guidebook.htm [accessed 
12 June 2007], 

U.S. OMB (U.S. Office of Management and Budget) (2007). 
Final Bulletin for Agency Good Guidance Practices, 

Section 1(3). Federal Register 72:16 (25 January 2007) p. 
3432. Available: 

http://www.whitehouse.gov/omb/fedreg/2007/012507 good 

guidance.pdf [accessed 6 December 2007], 


15 



















SECTION 2 


Elements to Be Considered in 
Study Conceptualization and Planning 


Consideration of the scientific and ethical 
approaches for observational human exposure studies 
begins at the very beginning of the study and continues 
throughout it. Because such studies involve human 
participants, researchers will have to consider the ethical 
issues associated with the regulatory requirements for 
human subjects review and approval. Beyond that, 
however, ethical principles and issues should be an 
integral part of all elements of the study and should be 
included as soon as a study is proposed. 

In laying out seven requirements for determining 
whether a research trial is ethical, Emanuel, Wendler, 
and Grady (Emanuel et al., 2000) listed the requirements 
in rough chronological order, from conception of the 
research to formulation of the plan and protocol to 
implementation of the research study. This section 
follows their outline as this document highlights areas 
that NERL exposure science researchers should consider 
as they develop plans for an observational human 
exposure study. Table 2-1 shows the ethical 
requirements and the topics in this section relevant to 
each requirement. 

The first stage in the research process is to 
understand the state of exposure science and EPA’s 
programmatic needs for exposure data. NERL scientists 
and managers must decide whether an observational 
human exposure study is necessary and justified to meet 
the Agency’s need. If so, then NERL staff will begin to 
plan for a study. A variety of important issues will need 
to be considered (identifying and enlisting stakeholders 
and community representatives, forming a research 
team, maximizing benefits for participants, precluding 
conflicts of interest, etc.). 

The planning phase will culminate in the 
development of a science-based study design in an 
ethically sound human subjects research protocol. 
Adhering to the principal that “Bad science is always 


unethical” (U.S. EPA, 2000), the research must first be 
judged to be scientifically sound to meet ethical 
standards. Peer review by independent and 
knowledgeable experts will be used by NERL to assess 
the scientific validity of its proposed research. But 
passing scientific peer review is just the first hurdle: 
sound science is not necessarily ethical. NERL’s 
observational human exposure studies also must meet 
both the ethical requirements set forth in human subjects 
regulations and the ethical standards demanded of 
responsible researchers by their peers and society. Peer 
review will focus on the study design and the science but 
also necessarily will incorporate relevant ethical 
considerations. IRB review will focus on ethics and the 
protection of the human research participants but also 
necessarily will incorporate evaluation of the adequacy 
of the study design and other relevant aspects of the 
science. The principle that unsound science is unethical 
science demands that exposure of human subjects to any 
research risk whatsoever, even minimal risk, cannot be 
justified if the research will not answer the scientific 
questions that motivated the research in the first place. 

After independent reviews evaluate both the 
scientific and ethical aspects of the proposed research, 
EPA policy requires that the proposed study undergo 
internal EPA review, and that the human subjects 
research protocol undergo evaluation by the Agency’s 
Human Subjects Research Review Official (HSRRO). 
The HSRRO, located in the EPA Office of the Science 
Advisor, ensures that Agency studies comply with the 
Common Rule and all directives of 40 CFR 26 providing 
guidance and principles to govern Federal agency 
sponsored human subject research.. Only after HSRRO 
approval can any research actually begin. As the NERL 
study is implemented, project data and concerns of the 
participants will be monitored on a continuing basis and 
compared with previously established standards and 


17 



Table 2.1. Seven Requirements for Determining Whether a Research Trial is Ethical 

From Emanuel, Wendler, and Grady (2000) 

Requirement 

Explanation 

Topics in this Section 

Social or 
scientific value 

Evaluation of a treatment, intervention, or theory that 
will improve health and well-being or increase 
knowledge 

Defining the study problem 

Justifying the study 

Identifying a research team 

Scientific validity 

Use of accepted scientific principles and methods, 
including statistical techniques, to produce reliable 
and valid data 

Study design 

Feasibility 

Sample size determination 

Representativeness of the sample 

Information collection rule 

Quality assurance 

Study design document 

Fair subject 
selection 

Selection of subjects so that stigmatized and 
vulnerable individuals are not targeted for risky 
research, and the rich and socially powerful are not 
favored for potentially beneficial research 

Ethical issues in fair subject selection 

Favorable risk- 
benefit ratio 

Minimization of risks; enhancement of potential 
benefits and risks to the subject are proportionate to 
the benefits to the subject and to society 

Designing in benefits for participants 

Assessing benefits and risks of study participation 

Independent 

review 

Review of the design of the research trial, its 
proposed subject population, and risk-benefit ratio by 
individuals unaffiliated with the research 

Scientific peer review 

Conflicts of interest 

Developing the protocol for ethical review 

Ethical review 

EPA review of scientific and ethical issues 

Informed 

consent 

Provision of information to subjects about the 
purpose of the research, its procedures, potential 
risks, benefits, and alternatives, so that the individual 
understands this information and can make a 
voluntary decision whether to enroll and continue to 
participate 

Informed consent 

Ensuring that participant behaviors are not adversely changed 

Respect for 
potential and 
enrolled subjects 

Respect for subjects by 

• permitting withdrawal from the research, 

• protecting privacy through confidentiality, 

• informing subjects of newly discovered risks or 
benefits, 

• informing subjects of results of the research, and 

• maintaining welfare of subjects 

Establishing criteria and standards for monitoring scientific and 
ethical issues during a study 


criteria to evaluate whether the study is on target for 
meeting its objectives, or if some unforeseen 
circumstances indicate that the study should be stopped 
immediately on either scientific or ethical grounds. 

2.1 Scientific Value of a Proposed 
Observational Human Exposure Study 

NERL’s planning for an observational human 
exposure study begins with an assessment of the state of 
exposure science and of EPA’s programmatic needs for 
exposure data. NERL scientists and managers must 
decide whether an observational human exposure study 
is necessary scientifically and whether it is justified to 
meet the Agency’s need. 


2.1.1 Defining the Study Problem 

Observational studies historically have been 
performed for many different purposes and in many 
different fields of research—social behavioral, 
economic, biological, medical, epidemiological, and 
exposure science. NERL has used observational human 
exposure studies to understand how people come into 
contact with pollutants in their everyday lives, with the 
ultimate goal of protecting public health. NERL’s 
exposure research program addresses critical science 
needs directly related to Agency goals for protection of 
human health. The research program is driven by key 
exposure science questions that may be generated from a 
number of different sources, including legislative 
mandates (e.g., the Food Quality Protection Act, the 


18 














Clean Air Act, the Safe Drinking Water Act), program 
offices or research planning groups in the Agency, 
scientific peers and researchers, or collaborators. 
Communities also may identify concerns about 
exposures in their locales. NERL’s observational human 
exposure studies collect data to improve exposure and 
risk assessments, to develop risk management strategies, 
and to substantiate informational and educational 
materials for use by EPA program offices (e.g., Office of 
Pollution Prevention and Toxic Substances, Office of 
Air and Radiation, Office of Children’s Health 
Protection). 

Emanuel et al. (2000) contend that an ethical 
research study must provide a worthwhile social or 
scientific value. Ideally, observational human exposure 
studies can provide both a scientific value and a social 
value to the participants and their community when 
feasible. Whenever possible, researchers should work 
with communities to develop studies that can help 
address community problems and maximize the benefit 
to the participants and the community, both of which 
also assume a burden for participation in a research 
study. 

The study problems addressed in past observational 
human exposure studies conducted or supported by 
NERL have varied substantially, as described in 
Appendix A of this document. As shown in Table A-l, 
NERL’s studies have addressed exposures to particulate 
matter (PM), air toxics, persistent organic chemicals, and 
nonpersistent chemicals including pesticides. The studies 
have examined single routes of exposure (air) and 
multimedia exposures, including dietary exposure. The 
studies range from small-scale pilot studies to large 
probability-based samples. They have included cross- 
sectional, longitudinal, and convenience samples. Table 
A-l demonstrates that many of the studies are small in 
scale and were intended to test a methodology to see if it 
may prove useful for a subsequent large-scale 
probabilistic human exposure research effort. Both 
small-scale and large-scale human exposure studies do 
involve human subjects. This means that the studies 
must meet both ethical standards and regulatory 
requirements. Regardless of the study’s scale, the 
scientific study design must be technically sound and 
appropriate to meet the objectives of the study. But the 
nature and objectives of the scientific inquiry will be 
different when the study is designed to test a 
methodology versus when the study is intended to 
measure a representative distribution of people’s 
exposures. Defining the study problem is a critical and 
fundamental first step in the scientific process, because it 


will establish the objectives that the research will be 
designed to achieve and the uses to which the research 
data will be put. The details of the scientific design of 
the study will naturally be strongly influenced by the 
objectives that the research is intended to meet. 

2.1.2 Justifying the Study 

Justification of any human study includes both a 
scientific and an ethical justification. In the list of seven 
ethical requirements that must be met for human subjects 
research to be considered ethically acceptable, four of 
those requirements, (1) respect for subjects, (2) informed 
consent, (3) favorable risk-benefit ratio, and (4) fair 
subject selection, are founded on the traditional ethical 
principles enunciated in the Belmont Report and 
codified in the Common Rule (Emanuel et al., 2000). 
But three requirements, (1) social or scientific value, 
(2) scientific validity, and (3) independent review, apply 
directly to the scientific aspects of the study. Similarly, 
Guideline 1 from the CIOMS (2002) document reiterates 
the foundational principle that “scientifically invalid 
research is unethical.” Beyond the traditional ethical 
expectations of respect for, protection of, and fairness to 
the research subjects, CIOMS requires investigators and 
sponsors to ensure that the research be “scientifically 
sound,” that it “conform to generally accepted, scientific 
principles,” and that all researchers be “qualified” and 

n 

“competent.” Text Box 2-1 identifies a number of 
elements that should be considered in justifying an 
observational human exposure study. As discussed 
below, a critical element to support justification of both 
the scientific and ethical elements of a study is the use of 
independent scientific and ethical peer review. 


7 Guideline 1 states “research can be ethically justifiable only if it is carried 
out in ways that respect and protect, and are fair to, the subjects of that 
research and are morally acceptable within the communities in which the 
research is carried out. Moreover, because scientifically invalid research is 
unethical in that it exposes research subjects to risks without possible benefit, 
investigators and sponsors must ensure that proposed studies involving human 
subjects conform to generally accepted scientific principles and are based on 
adequate knowledge of the pertinent scientific literature.” The commentary on 
the guideline goes on to say, “Among the essential features of ethically 
justified research involving human subjects, including research with 
identifiable human tissue or data, are that the research offers a means of 
developing information not otherwise obtainable, that the design of the 
research is scientifically sound, and that the investigators and other research 
personnel are competent. The methods to be used should be appropriate to the 
objectives of the research and the field of study. Investigators and sponsors 
must also ensure that all who participate in the conduct of the research are 
qualified by virtue of their education and experience to perform competently 
in their roles. These considerations should be adequately reflected in the 
research protocol submitted for review and clearance to scientific and ethical 
review committees.” 


19 



Text Box 2-1. Elements to be Considered in 
Justifying a Study 

• The research problem and questions to be addressed in the 
study 

• The objectives of the study or the hypotheses to be tested 

• A discussion of why human participants are required for the 
study, including a discussion of alternative designs that were 
considered 

• Available information on the need for the study (i.e., it is not 
redundant and the research question has not been already 
answered) 

• Available information from the scientific literature 
demonstrating the relevance of the proposed study 

• A discussion of the general technical approach and scientific 
soundness of the approach 

• An assessment of the needed competencies and 
qualifications of all personnel involved in conducting the 
research 

• The likelihood of success in meeting the study goals and 
objectives (including an evaluation of the accuracy, precision, 
and quality assurance of the data needed to attain the study 
goals and objectives) 

• Justification for the investment of time and money 


2.1.3 Identifying a Research Team 
To Plan and Implement the Study 

Once the study problem has been defined and 
justified, the next step in developing the research study 
is to form the research team. The team should be diverse, 
including the technical experts (e.g., exposure 
researchers, statisticians, chemists), stakeholders, and 
representatives and members of the community in which 
the study likely will be performed. Information on 
identifying potential conflicts of interest among 
researchers early in the planning stage is discussed in 
Section 2.5.2. For scientific, ethical, and practical 
reasons, the community should be appropriately 
involved throughout the study, including throughout the 
planning phase. Infonnation on identifying and engaging 
community members in the process is described in 
Section 6 of this document. The joint NRC-IOM 
committee reviewing ethical issues for research 
conducted in the homes and communities of the 
participants (like much of NERL’s human exposure 
research) concluded that “When researchers discuss a 
planned study with community representatives, 
understand their concerns and needs, and respond to 
them, protocols can be strengthened both scientifically 
and ethically” (p. xii, NRC & IOM, 2005). 

2.2 Ensuring Scientific Validity of the 
Research Study 

To facilitate scientific and ethical review, the 
research team members should develop a comprehensive 


and detailed study design that describes the technical 
approach for the observational study. Although the 
format and scope may vary depending on the specific 
study, there are a number of basic elements generally 
included in the study design. 

Translating the information developed in defining 
the problem and justifying the study into a real, 
workable, feasible study design and human subjects 
protocol is an iterative process involving input from all 
of the members of the research team. Scientific and 
technical expertise is required to assure the scientific 
integrity of the research, including developing the 
conceptual model s for the effort and devising a reliable 
sampling and analysis plan. Stakeholder input is critical 
to assuring that the generalizable research information 
from the study actually will be applicable for addressing 
the study problem. Community input is particularly 
important during the planning stage because the 
community representatives can provide valuable 
information about the community members (the future 
study cohort), the cultures of the community, community 
values, community concerns, feasibility of working in 
the community, infonnation needed to develop the 
technical approach, and information on important factors 
like pollutant sources and other stressors in the 
community. (Additional considerations for 
communicating and working with both the participants 
and the community in which they live are the topics of 
Sections 5 through 7 of this document.) 

In developing the study design and the human 
subjects protocol, the research team often will have to 
deal with a variety of complex issues, including how to 
maximize benefits for participants, the community, and 
the stakeholders, and how to ensure the integrity, 
generalizability, and representativeness of the study. 

2.2.1 Study Design 

In epidemiology, the concept of study design has 
been structured to include (1) experimental studies, like 
drug trials, where the variables are isolated and 
controlled (See discussion on experimental studies in 
Appendix A.) and (2) observational studies where the 
variables are not controlled intentionally, but are simply 


A conceptual framework or model is often an effective approach to describe 
the relationship between the predicted exposures of the population and the 
population stressors, laying out the predicted pathways and routes of exposure 
(e.g., see Cohen Hubal et al., 2000). A conceptual model often is illustrated by 
a block diagram that represents the major scientific processes and interactions. 
The model is often very useful in developing an analysis plan that describes 
the hypotheses or objectives of the study, identifies the data needed to address 
the objectives, and specifies the analyses that will be done to test the 
hypotheses or address the objectives. 


20 





observed along with the outcome or response measures. 
Clearly, the NERL human exposure observational 
studies (see Table A-l) fall into the latter category. Such 
studies may be cross-sectional studies (where a subset of 
the population is observed at the same time); cohort 
studies (which measure the same variables and response 
measures in a group of people repeatedly over time); 
case control studies (where the observed population is 
separated into two groups based on the outcome or 
response measure [the case group and the control group], 
and exposure variables between the two groups are 
analyzed for differences); or studies that combine 
approaches. The research may collect data from the 
participants once (e.g., in a large-scale, randomized 
design to collect a representative sample of the 
population, like many of the National Human Exposure 
Assessment Survey [NHEXAS] studies); over a few 
days (e.g., NERL’s Particulate Matter [PM] panel 
studies); from a cohort in different seasons or years (e.g., 
NERL’s Detroit Exposure Aerosol Research Study 
[DEARS]; the NHEXAS study in Maryland); or a series 
of cross-sectional studies repeated one after another with 
a different group of participants each time. (This latter 
case often is necessitated to minimize time and expenses 
associated with being in the field and because of 
limitations of sampling equipment or field technicians to 
assist in the collection of the data.) 

Although much of the literature on study design 
involves experimental studies (like drug trials), there is 
much that can be learned about the design of 
observational studies in epidemiology, including 
understanding their strengths and weaknesses. Web sites, 
like “Epidemiology for the Uninitiated” (Coggin et al., 
1997, available at www.bmj.com/epidem/epid.html ), 
provide useful basic information on important topics for 
observational studies and their design. 

The specific details of the study design and the 
sampling approach to be used will depend very much on 
the objectives to be achieved in the study. Based on the 
objectives, a good study design must first clearly state 
the research question (or hypothesis to be tested) and 
must also define in advance what outcome or response 
measure will be used to test the question or hypothesis. 
Study designs that are vague or which propose to test 
some outcome measures against a variety of potential 
factors do not represent sound science. Statistically, a 
correlation is likely to be found between an outcome and 
some factor if enough factors are tested—whether there 
is an actual biological or physical relationship or not. 
This highlights the importance of statistics as an integral 
part of the study design process. Including individuals 


with appropriate statistical knowledge and experience on 
the research team from its very beginning is critical to a 
scientifically sound study design. (See, for example, 
Dallal, 2001, “Some Aspects of Study Design” in The 
Little Handbook of Statistical Practice at 
www.StatisticalPractice.com . and at www.tufts.edu/-gda 
llal/LHSP.HTM ). 

The study design must carefully consider each item 
of data or information that is to be collected during the 
study and how the data will be used in the analysis. All 
of the data needed to complete the analysis and test the 
hypothesis must be collected, otherwise the research 
objectives cannot be met, and the study should not go 
forward. Alternatively, data that are unrelated to the 
study analysis should not be collected. Collection of 
such data imposes a burden on both the participants and 
research staff with no known potential for benefit. 
Collecting, validating, and archiving such data wastes 
time and money and inappropriately burdens the 
participants. If there is no solid analysis plan for a 
particular data item, such data should not be collected. If 
the researchers actually believe that some factor may 
represent a potentially overlooked variable, then they 
should collect the information to test that hypothesis 
correctly. But, just collecting the data “while we can,” 
with no plan for how to analyze and use the data, wastes 
resources, imposes unnecessary burden, and often proves 
tempting as a statistical correlation hunt. Finally, the 
study design must be described in sufficient detail to be 
properly evaluated. Preparation of the study design 
document is described in a later section, but the 
overriding goal is to provide enough information to 
allow proper review of the science behind the study 
design by the research team, the scientific peer 
community, and the IRB panel members. 

2 . 2.2 Feasibility 

The authors consider the evaluation of the feasibility 
of accomplishing the study to be one of the most critical 
components of the development of the study design. 
Evaluating the feasibility of the research project involves 
considering not only whether there are sufficient 
resources to accomplish the study, but whether or not the 
study is feasible from a scientific and ethical perspective. 
If the research team concludes that the study is not 
feasible, there will be no further effort to develop the 
study. There may be practical limitations that preclude 
conduct of the study as initially conceived. Because 
“scientifically invalid research is unethical” 
(Guideline 1, CIOMS, 2002), it is essential that scientific 
and ethical considerations be considered together. Text 


21 










Box 2-2 includes some examples of the types of 
questions that may be asked when evaluating the 
feasibility of a study. 


Text Box 2-2. Is the Study Feasible? 

• What are the sample size requirements? Can enough 
participants be enrolled into the study from the proposed 
community, considering the eligibility criteria and anticipated 
response rate? What is the predicted retention rate if this is a 
repeated measurements study? Is that acceptable? 

• Is the research question well defined, and can we measure the 
variables and the outcome metrics? 

• Are the measurement methods specific and accurate enough 
to accomplish the research? 

• Does the analysis plan provide results to test the research 
questions and to meet the study objectives? 

• Will the community be receptive to this study? 

• Are there cultural mores, societal values, or other factors 
associated with the community that would make it difficult to 
conduct the study in the community? Is the study morally 
acceptable to the community? 

• Is there a community structure that will allow the research 
team to engage the community in the study? 

• What is the burden on the community? 

• What is the burden on the participants? Is it acceptable? 

• What is the risk-benefit balance? Is it acceptable, considering 
the burden on the participants? 

• Are there sufficient resources available to conduct a study of 
this size? 

• Are resources available for community outreach and sustained 
interactions with the community? Are resources available to 
support community members involved in the study? 

............ 


2.2.3 Sample Size Determination 

One critical issue in assuring that an observational 
human exposure study is scientifically valid (and, 
thereby, not invalid and unethical) is the issue of sample 
size. EPA’s Science Advisory Board has stated, “Bad 
science is always unethical; research protocols that are 
fundamentally flawed, such as those with sample sizes 
inadequate to support reasonable inferences about the 
matter in question, are unjustifiable” (p. 2, U.S. EPA, 
2000 ). 

A study has to have an adequate size to meet the 
study objectives. If the sample size is too small, the 
results may not be statistically significant, and the results 
may not be either valid or generalizable. Such a result 
would be a waste of resources or cause undue burden on 
study participants without generating the intended 
generalizable knowledge that will benefit society. On the 
other hand, if the study sample size is larger than 
necessary to meet a study objective, this also may result 
in a waste of resources or the imposition of needless 
burden on participants. 


Sample size determination is an important step in 
planning a study, but it can be a difficult task (Lenth, 
2001). Sample size determination also may be 
confounded by other issues that will reduce the number 
of measurements that may be used in the analysis. For 
example, participants in a longitudinal study may “drop 
out” over time (some may move, others may tire of 
participation, etc.), so that the number of participants at 
the end of the study will be less than the number that 
started the study. The study design must account for the 
attrition of participants over time and plan ahead to 
recruit enough participants to ensure that a statistically 
useful number of participants complete the study. Often 
NERL scientists have used historical retention rates to 
estimate the sample size needed for a study. (See 
discussion of retention rates in NHEXAS publications.) 

in addition, some participants or their environments 
may not have concentrations above the detection limit. 
Depending on the nature of the research question, data 
below the analytical detection limit may, or may not, be 
useful in addressing the research question: sample size 
may need to be increased to account for missing values 
and values below detection. Pilot studies and 
environmental studies (with no participants as human 
subjects) may prove useful in understanding the range of 
concentrations to be expected and may provide insight 
into how to adjust the sample size appropriately. In 
surveys, like NERL’s National Human Activity Pattern 
Survey (NHAPS) for example, some randomly selected 
participants simply may refuse to participate, decreasing 
the number of samples and perhaps biasing the data. 

It is critical that sample size be determined at the 
time of study conceptualization and planning and not 
after the study already has been conducted. Researchers 
must include experts with the appropriate statistical 
expertise on the research team at its very inception. For 
additional information and insight, readers should refer 
to biostatistics books, Web sites, and other references 
(Lenth, 2001; Castelloe, 2000; Kraemer and Thiemann, 
1987; Van Belle and Fisher, 2004; Wackerly et al., 2001; 
Dallal, 2001) about this very important topic. 

2.2.4 Representativeness of the Sample 

In addition to concerns about the sample size being 
sufficient to provide statistically significant results, 
researchers also must be concerned about the individuals 
who participate in a study and of what group or 
population they may be representative. Research, as 
defined in the Common Rule, is “a systematic 
investigation ... designed to develop or contribute to 
generalizable knowledge.” How “generalizable” the 


22 






results of an observational study may be depends on the 
representativeness of the sample (the participants). A 
review of former NERL studies (Table A-l) shows a 
wide variety of approaches to selecting the participants, 
both probability sampling and nonprobability sampling. 
Some of the studies have involved randomized sampling 
(e.g., NHAPS, NHEXAS), selecting a cohort of interest 
and then using a randomized sample (e.g., Children’s 
Total Exposure to Persistent Pesticides and Other 
Persistent Organic Pollutants [CTEPP], DEARS) or a 
convenience sample (e.g., some panel studies), 
purposeful selection (judgment sampling) by the 
research team (for methods testing studies), recruiting 
the whole population in a locale or of a particular cohort 
(e.g., as proposed for the National Children’s Study 
[NCS]), or simply a convenience sample (in small pilot 
studies). 

The approach used to select the participants has 
depended on the objectives of the study. Research to 
understand and describe the distribution of exposures in 
the general population (like NHEXAS) or of the 
population or cohort in a particular state or region (like 
CTEPP or Agricultural Health Study [AHS]), has 
required a large number of randomly-selected 
participants. Randomized selection is recognized as a 
valid statistical method to get a sample that is 
representative of the larger population from which the 
participants were selected. Pilot studies performed to 
evaluate a method or to estimate the likely range of 
exposure concentrations often have employed either 
purposeful sampling, where the researchers use 
information on the relevant characteristics of the 
population to select those participants who will exhibit a 
wide range of activity levels or potential exposure 
concentrations, or convenience sampling, where the 
researchers select the most accessible members of a 
population 

NERL’s observational human exposure studies also 
have routinely collected information about the 
participants’ activities by using questionnaires and 
surveys. Survey design is both a science and an art 
because the design of surveys is based on statistics and 
science, but designing a good and effective questionnaire 
is often an art that requires understanding the individuals 
being surveyed. Text Box 2-3 identifies some of the 
areas of art involved in designing an effective 
questionnaire. 

Understanding the process for selecting participants 
and the statistical-scientific requirements of 
questionnaire design are both components of survey 
sampling and design. A variety of references can provide 


the researcher with information about the issues in 
survey sampling and design. (See 
http://home.ubalt.edu/ntsbarsh/Business-stat/stat- 
data/Surveys.htm and www.statpac.com/surveys/ , for 
example.) But the research team must include or have 
access to the appropriate survey statistics expertise as it 
plans the research study. 


Text Box 2-3. Questionnaire Considerations 

• Questions should be simple and in a language the individual 
can understand. 

• Questions should be unambiguous. 

• Questions should be relevant to the study. 

• Questions should not be too personal. 

• The questionnaire should be as short as possible. 

• The questions should not be leading (e.g., internally 
suggestive of the answer). 

• Questions should follow a logical order. 


2.2.5 Information Collection Rule 

As Federal employees, NERL researchers also must 
be aware of Information Collection Rule requirements. 
The Paperwork Reduction Act stipulates that every 
Federal agency must obtain approval from OMB before 
collecting the same or similar information from 10 or 
more members of the public. An Information Collection 
Request (ICR) is required if the same or similar 
information is being collected from 10 or more non- 
Federal respondents within a 12-month period, even if 
the information collection is voluntary. Generally, any 
survey, questionnaire, monitoring, reporting, or 
recordkeeping requirement imposed on non-Federal 
respondents by EPA will require an ICR. Information 
collections associated with all cooperative agreements 
funded by the EPA require an ICR. When an ICR is 
required, it must be approved by OMB before the 
collection begins, regardless of whether the collection of 
information is mandatory, voluntary, or required to 
receive a benefit. The principal investigator must prepare 
an ICR and submit it to the appropriate Office of 
Environmental Information Desk Officer. 

An ICR 

• describes the information to be collected, 

• provides justification for why the information is 
needed, and 

• estimates the time and cost for the public to answer 
the request. 

Information about ICRs and their requirements is 
available to NERL and other EPA staff members at 
http://intranet.epa.gov/icrintra/index.html . 


23 











2.2.6 Quality Assurance Project Plan 

Data of unknown or uncertain quality can undermine 
the scientific integrity of a study and render an otherwise 
sound study invalid. NERL scientists must be diligent in 
the implementation of the procedures and processes 
specified in a well-developed quality assurance project 
plan (QAPP). A discussion of quality assurance 
programs and QAPPs is outside of the scope of this 
document. There are many good references on the topic, 
including the EPA Web site, www.epa.uov/quality/ . 

2.2.7 The Study Design Document 

The study design document should contain sufficient 
detail to allow independent review and assessment of the 
scientific soundness of the study and the approaches that 
will be followed to ensure that the study meets the 
highest scientific and ethical standards. The research 
team can meet regularly to specifically evaluate the plan. 
It should be noted that a study design is not the same as 
an implementation plan. The latter includes an even 
greater level of detail describing how the study will be 
performed and includes protocols and operating 
procedures. Text Box 2-4 lists a number of elements that 
may be appropriate to include in a study design. 

2.3 Ethical Issues in Ensuring 
Fair Subject Selection 

One of the ethical principles of human subjects 
research is that selection of participants should be fair. In 
Section 2.2.4, the discussion centers on understanding 
what population or cohort the participants in a research 
study represents, and how such a selection may be 
influenced by the research questions and study 
objectives. That consideration actually represents the 
first component of ensuring that subject selection is fair. 
That is, the scientific goals of the study should be the 
primary basis for determining what groups or individuals 
should be recruited and enrolled in a study. Participants 
should not be recruited either because of privilege or 
because of vulnerability or their inability to look out for 
their own interests properly. Similarly, groups or 
individuals should not be excluded peremptorily without 
consideration of the risks and benefits to them as 
individuals. Section 3 of this document discusses 
protection of vulnerable groups and concludes that 
NERL researchers should include vulnerable groups in 
observational human exposure studies only if their 
participation is critical to the success and applicability of 
the research. Even then, EPA and NERL researchers will 
have to meet stringent standards for protecting the rights 
and safety of the vulnerable participants. “The essence of 


Text Box 2-4. Elements That May Be Included in a 
Study Design 

• Introduction and background, including the purpose and scope 
of the study 

• The desired outputs and outcomes of the study, including the 
objectives and the hypotheses to be tested 

• A brief description or overview of the study 

• The technical approach and conceptual model that accounts for 

sources of the chemicals being studied; 
potential routes and pathways of exposure; 
factors that may impact exposure and other relevant 
stressors; 

selection and characteristics of the study participants; 
eligibility criteria; and recruitment, retention, and payment 
approaches; 

justification for sample size, the methodology for selecting 
participants, and the sampling methods; 
characteristics of the community in which the study will be 
performed; 

environmental conditions, factors, or end points to be 
measured, including sampling and analysis approaches and 
methods (with description of expected performance); 

survey design and questionnaires and other survey 

instruments, as applicable (with description of prior use and 

validation in similar studies); 

pilot studies that may be undertaken: 

quality assurance project plan and quality control; 

timeframe for the study; 

exposure scenarios to be considered; 

burden of the study on the participants; 

resources available; and 

feasibility 

• Discussion of alternative study designs and approaches 
considered and reasons for rejecting other approaches and 
selecting the one proposed 

• An analysis plan that considers 

Information and data needs, including data storage, security, 
access, and release; 

nature of the measurement data (e.g., variability, quality 
assurance); 

how the collected data will be used, and how the proposed 
analyses will address objectives of the study; and 
hypotheses to be tested and statistical power and sample 
size required to test the hypotheses 

• Resources required or available 

• Project organization and management, including team members 
and roles and responsibilities 

• Schedule 


fairness in human subjects research is that scientific 
goals, considered in dynamic interaction with the 
potential for and distribution of risks and benefits, 
should guide the selection of subjects.” (Emmanuel et al, 
2000). On the other hand, as discussed in Section 3, 
many study problems specifically address exposures of 
vulnerable groups to chemicals and other stressors. 
Researchers should not avoid research studies that will. 


24 












of necessity, include vulnerable groups to address the 
study hypotheses or objectives simply to avoid the more 
stringent requirements for working with these groups. 

! 

2.4 Ensuring a Favorable Risk-Benefit Ratio 

2.4.1 Designing in Benefits for the Participants 

Study designs vary depending on the objectives of 
the study, existing knowledge on the research question, 
and the hazard being studied (NRC & IOM, 2005). 
Recent ethical discussions about study designs in human 
subjects research (cf., Recommendation 7.1, p. 143, 
NRC & IOM [2005] and Emanuel et al. [2000]) support 
the development of innovative study designs to 
maximize the benefit 9 to the study participants, as well 
as to the community and the greater society beyond. 
Observational human exposure studies generally collect 
data that contribute to generalizable knowledge that will 
benefit the community and society as a whole, but they 
often do not provide obvious direct benefit to study 
participants. Therefore, it is important to include 
elements in the study design that can offer benefits to the 
participants wherever possible. This is not always 
straightforward, but one way that participants, as well as 
communities, can benefit from these studies is by 
incorporating strong educational components into the 
conduct of the research. For example, brochures, videos, 
and other materials that educate study participants on 
safety around the home or on how to reduce their 
exposure to chemicals can be distributed during the 
study. EPA’s program offices, including the Office of 
Children’s Health Protection, the Office of Pollution 
Prevention and Toxics, the Office of Pesticide Programs, 
the Office of Drinking Water, and others have Web sites 
with substantial amounts of informational and 
educational materials available that could be distributed 
to study participants. Other organizations, such as the 
American Lung Association, the American Cancer 
Society, the American Academy of Pediatrics (AAP), 
and various environmental groups, have materials of 
which study participants may not be aware that could be 
used as educational materials when relevant. 

In addition, approaches that provide direct benefits 
to study participants will need to be tailored to the 
particular study population and community. Feedback 
from potential participants in focus groups and input 
from community representatives may be useful in 
identifying these approaches. 


9 Payment to participants is never considered a benefit of a study. 


2.4.2 Assessing Benefits and Risks of Study 
Participation 

For all research involving human participants, the 
Common Rule requires researchers to ensure that 
potential risks “are reasonable in relation to the 
anticipated benefits,” and that risks are minimized (40 
CFR 26.111). It is most useful if the assessment of 
benefits and risks is begun early in the scoping and 
planning phase of a study. 

Unlike some biomedical research that involves the 
study of interventions or procedures that hold out the 
prospect of direct diagnostic, therapeutic, or preventative 
benefit for the study participants, observational human 
exposure studies often do not have a similar prospect of 
direct benefit to the participant. Therefore, the risk- 
benefit balance is based on the balance between the risks 
to the participants and the expected benefits to society 
(generalizable knowledge). The risks to participants 
must be reasonable [40 CFR 26.111(a)(2)] in relation to 
the importance of the knowledge gained. This 
assessment of the risk-benefit balance, therefore, needs 
to be performed in the initial planning of the study to be 
included in the justification for the study (Section 2.2). 

If there is no prospect of direct participant benefit, 
and the study participants are children, moreover, EPA is 
permitted to conduct or support only those observational 
human exposure studies that meet both the regulatory 
definition of “observational” and the regulatory 
definition of “minimal risk.” The latter is defined in the 
Common Rule at 40 CFR 26.102(i) and reiterated in 
Subpart D of the EPA Rule at 40 CFR 26.402(g): 
“Minimal risk means that the probability and magnitude 
of harm or discomfort anticipated in the research are not 
greater in and of themselves than those ordinarily 
encountered in daily life or during the performance of 
routine physical or psychological examinations or tests.” 
In applying this definition, EPA adheres to the 
consensus standard that the reference population for this 
definition is normal children living in safe, healthy 
environments. In its discussion of the perception of risks 
and benefits, the NRC & IOM (2005) report on housing 
health hazards in children notes that the children 
participating in these studies may be at risk for physical 
harms or adverse health outcomes because they live in 
housing (or otherwise occupy environments) with health 
hazards. However, such risks are not introduced by the 
research but, rather, would be present whether or not the 
children were involved in a research study. As a 
consequence, the study still would meet the regulatory 
criteria for minimal risk as long as the research itself 
introduced no risks over and above those minimal risks 


25 





experienced by normal children living in safe healthy 
environments. 

However, the existence of greater than minimal 
background risks that are not introduced by the research, 
nonetheless, raises additional ethical considerations. The 
joint NRC & IOM Committee on Research on Housing- 
Related Health Hazards Involving Children discussed 
the ethical arguments that arise when scientists conduct 
research that observes children in poor-quality housing. 
They point out that a researcher’s first duty of 
beneficence under the Common Rule requires that the 
risks of the research actions be proportionate to 
[“reasonable in relation to”; 40 CFR 26.111(a)(2)] the 
benefits of the research, and that the risks be minimized. 
They acknowledge, however, that some have argued that 
the “best interests of the child” also obligates researchers 
to “rescue” children from harm and to provide better 
living conditions. They conclude that, properly applied, 
the ethical principle of beneficence does indeed direct 
researchers who observe serious harms to child subjects 
to take steps to try to prevent the harms. However, they 
also argue that the researcher’s duty does not extend to 
“personally and directly prevent harm by removing the 
child from the harmful environment” (p. 60, NRC & 
IOM, 2005). They conclude instead that “it is unrealistic 
and unfair to hold individual research investigators 
responsible for ameliorating the social circumstances 
that they study” and that “a nuanced balancing of the 
benefits and risks of research” is an ethically sound 
approach that is firmly established in Federal regulations 
(p. 60, NRC & IOM, 2005). Balancing the ethical 
obligation to mitigate risks or harms observed during 
research with the reasonable limits on an investigator’s 
moral responsibility for the social circumstances 
surrounding the research will be the subject of later 
sections of this document, particularly Section 4.3.1. 

Assessing the risks and benefits of the research 
study can be very difficult for the researchers, especially 
because the researchers and the community or 
participants may perceive the risks and benefits quite 
differently. (See the discussion in NRC & IOM [2005], 
for example.) To understand the community’s 
perspective better, the researcher may find it helpful to 
discuss the assessment of risks and benefits with 
members of the research team, community 
representatives, and relevant stakeholders. The research 
team should consider the use of a community advisory 
board (CAB) to provide input to the assessment of the 
risks and benefits of the study. The group could include 
individuals who are representative of the population to 
be studied, community representatives, exposure 


scientists, and bioethicists. The group should include 
experts familiar with the human subjects research 
regulations, preferably including someone who has 
served on IRBs. Obtaining input from the group can be 
accomplished by submitting the study concept and 
general study design to the group for review and 
feedback, even before a full study design has been 
developed. (See the discussions of CABs in Sections 5 
and 6.) Ultimately, it will be the review by the members 
of the IRB that will determine whether the balance is 
appropriate and justifiable. 

2.5 Independent Scientific and 
Ethical Review 

Because issues of science and ethics are intrinsically 
bound together in human subjects research (Emanuel et 
al., 2000; CIOMS, 2002), it is important that scientific 
and ethical reviews be considered together, not 
separately. Scientific reviews are performed to ensure 
the scientific soundness of the study, whereas ethical 
reviews are performed to ensure proper action and the 
protection of the human subjects in a research study. A 
study that is not scientifically sound could expose study 
participants to unnecessary risk or inconvenience and 
burden, with no additional societal benefits (i.e., no 
increase in generalizable knowledge). EPA’s Science 
Advisory Board has stated that “bad science is always 
unethical” (U.S. EPA, 2000), and CIOMS declares that 
“scientifically invalid research is unethical” (CIOMS, 
2002). 10 It is clear, therefore, that the ethical review has 
to consider the scientific aspects of the study also. 

There may be multiple levels of review during 
development of the study design and human subjects 
research protocol for an observational human exposure 
study. The research team is responsible for the design of 
the study and for ensuring that adequate peer review is 


CIOMS (2002) Guideline 2 asserts “Ethical review committees—All 
proposals to conduct research involving human subjects must be submitted for 
review of their scientific merit and ethical acceptability to one or more 
scientific review and ethical review committees. The review committees must 
be independent of the research team, and any direct financial or other material 
benefit they may derive from the research should not be contingent on the 
outcome of their review. The investigator must obtain their approval or 
clearance before undertaking the research. The ethical review committee 
should conduct further reviews as necessary in the course of the research, 
including monitoring of the progress of the study." The CIOMS document 
continues, “According to the Declaration of Helsinki (Paragraph 11), medical 
research involving humans must conform to generally accepted scientific 
principles, and be based on a thorough knowledge of the scientific literature, 
other relevant sources of information, and adequate laboratory and, where 
indicated, animal experimentation. Scientific review must consider, inter alia, 
the study design, including the provisions for avoiding or minimizing risk and 
for monitoring safety. Committees competent to review and approve scientific 
aspects of research proposals must be multidisciplinary." 


26 



performed to evaluate both the scientific and ethical 
approaches for the study. Following completion of a 
draft study design, researchers should engage a diverse 
group of experts to review the study design and human 
subjects aspects. The scope of the study should dictate 
the level of the review (i.e., internal or external 
independent peer review). A small pilot study to 
evaluate measurement methods or to collect screening 
level data in preparation for a large study may not 
require as extensive review as a larger study. 

When the scientific soundness of the study has been 
evaluated and found to be feasible, and the final study 
design is completed, the human subjects research 
protocol should be developed and submitted to the IRB 
for review and approval. For studies conducted or 
supported by EPA, additional review and certification of 
the human subjects research protocol is required by EPA 
Order 1000.17 Al. (available online at 
www.epa.gov/oamrtpnc/forms/1000 17a.pdf ). Review 
and approval of the protocol and associated documents 
must be obtained from EPA’s HSRRO, located in the 
EPA Office of the Science Advisor, before any work 
begins. Any changes made to the protocol after IRB 
approval must be submitted to and approved by the IRB. 

2.5.1 Scientific Peer Review 

For all studies, regardless of the scope, the research 
team should solicit review and comment on the scientific 
approach by experts external to the research team. A 
peer review panel consisting of individuals who were not 
involved in the design of the study can be formed to 
review the scientific soundness of the study. It is 
important for the panel to consist of individuals with 
experience and background appropriate to the study and 
to include members with knowledge of the ethical 
principles for protection of human subjects in these types 
of studies. The panel also would benefit from including 
someone with sufficient background and expertise in 
statistics to evaluate whether the study design, sample 
size, and proposed data analyses are appropriate and 
adequate to address the study objectives or test the 
hypotheses. For small studies, the peer review panel may 
consist of individuals within the organization conducting 
the study if they have not been involved in developing 
the study design. For larger and complex studies, it is 
recommended that an external peer review panel be 
convened to review both the scientific and ethical 
soundness of the study design. 

For research conducted or sponsored by NERL, 
human subjects research efforts will undergo both a 
scientific review and an ethical review. The director of 


the division conducting or funding the observational 
research is the manager with the primary responsibility 
for ensuring that the scientific and the ethical reviews are 
conducted, and that the review comments are properly 
addressed. The study design will be reviewed for 
scientific quality by independent and knowledgeable 
reviewers. Depending on the scope of the study, the 
appropriate NERL associate director or the NERL 
laboratory director will make the final determination 
about (1) the process for selecting scientific peer 
reviewers (including the range of disciplines to be 
included), (2) the nature and scope of the review process 
(e.g., charge to the reviewers and scope of the review; 
letter reviews, convening a peer panel, or both; the size 
and nature of the panel review; etc.), and (3) the 
adequacy of the responses to the scientific review. 

2.5.2 Conflicts of Interest 

It is recommended that potential conflicts of interest 
among researchers or study participants be identified at 
all stages of study planning and implementation, but 
particularly early in the study during the planning stage. 
There can be many sources of potential conflicts of 
interest, including sources of project funding, pressures 
to publish, consulting arrangements of the investigators, 
employment of investigators’ family members with 
affected parties, participation in affected advocacy 
groups, collaborations or relationships with experts on 
the IRB or other independent review committees, 
institutional conflicts for any contractors who may be 
involved, or a wide range of other situations. 

Any situations that constitute actual conflicts of 
interest and all potential or apparent conflicts of interest 
must be reported to the IRB for their review and 
resolution. The CIOMS (2002) guidelines for research 
protocols involving human subjects specify that all 
sponsors of the research be identified, and that the 
protocol include actions to disclose and address potential 
conflicts of interest. Concerns about conflicts of interest 
also need to be identified and discussed with the 
researchers, community, and other stakeholders to make 
a determination of the existence of conflicts, and how 
they should be avoided or handled. 

Even if actual conflicts of interest do not exist, 
researchers should recognize that there can be perceived 
conflicts of interest that can be just as damaging as real 
conflicts of interest. Perceptions by participants, 
community members and representatives, stakeholder 
groups, and the public may be substantially different 
from the reality of the situation. This is especially likely 
to occur when external sources, such as industry, are 


27 



involved in funding research. Even though researchers 
may develop agreements with funding organizations that 
ensure researcher autonomy, a perception may exist that 
the funding organization will bias the study (Resnik and 
Wing, 2007). Concerns about perceived conflicts of 
interest should be discussed with the IRB and other 
relevant review committees, in addition to the 
researchers, the community, and other stakeholders. The 
IRB must be made aware of any circumstances that may 
give rise to actual conflicts of interest or to the 
appearance or perception of a conflict of interest. The 
IRB's recommendations about how to resolve any such 
conflicts must be strictly adhered to by NERL 
researchers. 

2.5.3 Develop the Human Subjects 
Protocol for IRB Review 

IRBs may have specific format requirements for 
their human subject research protocols. Traditionally, the 
human subjects research protocols for research 
conducted or funded by NERL have included 
descriptions of the project, including title and description 
of the research; the duration of the project; the type of 
data to be collected; the objectives of the study; the 
number of samples; a description of the participants and 
participant recruitment procedures; the informed consent 
procedures and forms; estimates of participant risk and 
burden, an assessment of benefits and the risk-benefit 
ratio; and actions to protect the participants. CIOMS has 
developed a comprehensive list of items that they 
recommend for inclusion in a human subjects research 
protocol (Appendix 1, CIOMS, 2002). Many of the 
items that they identify are also useful for observational 
human exposure studies. (The CIOMS items can be 
found in Appendix C of this document.) The authors 
recommend that anyone developing a human subjects 
protocol for observational human exposure studies 
review and utilize the CIOMS list of topics, as 
appropriate. Text Box 2-5 identifies a number of topics 
that should be considered in development of the human 
subjects research protocol. 

In addition, the authors’ experience leads them to 
suggest that three additional topics beyond those from 
the CIOMS (2002) document also may need to be 
considered in a human subjects protocol: (1) approaches 
to minimize changes in participant behavior because of 
participation in the study (see Section 2.3.4); 
(2) approaches to minimize therapeutic misconception 
(see Section 5.4.1); and (3) actions to involve the 
community in a community-based participatory research 


Text Box 2-5. Potential Topics in a 
Human Subjects Research Protocol 

1. Title 

2. Summary in lay language 

3. Justification for the study 

4. Ethical issues and proposed resolution 

5. Summary of previous research 

6. Affirmation of Belmont Principles and 40 CFR 26 compliance 

7. Previous history or use of the protocol 

8. Information on the location and demographics of research 

9. Information on funding organization, researcher partners, 
and collaborators 

10. Names, qualifications, and experience of investigators 

11. Objectives, hypotheses, assumptions, and variables 

12. Study design 

13. Sample size and power and statistical analysis plan 

14. Criteria and justification for subject selection 

15. Justification for use of vulnerable groups, if any 

16. Process of recruitment 

17. Actions to involve the community in a community-based 
participatory research program 

18. Description and explanation of any and all interventions 

19. Measurements or data to be collected 

20. Any clinical or other tests 

21. Rules or criteria for removing subjects or terminating the 
study 

22. Adverse events and unanticipated problems—reporting and 
responses 

23. Potential benefits to subjects or others 

24. Expected benefits of the research to the population 

25. Informed consent process and responsibilities 

26. Protections for the consent/assent of vulnerable participants 

27. Efforts to minimize “therapeutic misconception” 

28. Approaches to minimize changes in participant behavior 

29. Payments 

30. Plans for informing subjects about items that could affect 
subjects’ willingness to continue in the study 

31. Plans to inform subjects about the results of the study 

32. Privacy and confidentiality 

33. Security of personal information and when, how, and by 
whom private information can be revealed 

34. All foreseen uses of personal data or biological materials 

35. Procedures for data and safety monitoring and oversight of 
the study and the criteria for identifying, reporting, and 
responding to adverse events, including ethical breaches, 
environmental measures in excess of reporting standards, 
and collateral observations, and criteria for prematurely 
terminating the study if necessary 

36. A list of the references cited in the protocol 

37. The source and amount of funding 

38. Protocols for dealing with financial or other conflicts of 
interest 

39. Schedule 

40. Arrangements with sponsors regarding publication rights and 
procedures 

41. Reasons for not publishing the study findings 

42. Procedures for preventing falsification of data 


28 







(CBPR) effort, as appropriate (see Section 6, especially 
Section 6.10). 

2.5.4 Ethical Review 

In the United States, ethical reviews of studies 
involving human subjects are performed by IRBs. The 
Common Rule specifies requirements (40 CFR 26.107 - 
115) for IRB membership, IRB functions and operations, 
IRB review of research, and other details related to IRB 
review and approval of research. Emanuel states that 
“the independent ethical review of [human subjects 
research] should involve individuals with training in 
science, statistics, ethics, and law, as well as reflective 
citizens who understand social values, priorities, and the 
vulnerability and concerns of potential subjects” 
(Emanuel et al., 2000). It is beyond the scope of this 
document to include detailed discussions on IRB 
membership, operations, processes, etc. The reader is 
referred to the Common Rule, as well as a number of 
other available references (e.g., OHRP, 2007; CFR, 
2006; U.S. HHS, 1993; NRC, 2003). 

It is essential that research with human subjects be 
carried out or strictly supervised by suitably trained, 
qualified, and experienced investigators. For all research 
subject to the Common Rule, these qualified researchers 
are expected to prepare a human subjects research 
protocol (as in Section 2.5) and to submit the protocol to 
be ethically and scientifically appraised by one or more 
suitably constituted IRBs, independent of the 
investigators. 

There are a number of other issues associated with 
IRBs that may impact researchers conducting 
observational human exposure studies. As an example, 
there has been concern about the transparency of IRBs. 
Questions have been raised about what information the 
IRB should make available to the public regarding 
membership on the IRB for review of individual 
projects, the discussions held with the researchers, the 
IRB’s concerns about the research protocol, the 
researchers’ response, etc. Should this information be 
documented in files that the researchers can make 
available to the participants, community, stakeholders, 
and the public? At the present time, there is no clear 
approach as to how to address these issues. Because 
these issues are associated with the IRB, not the 
researcher, it is outside the scope of this document to 
recommend approaches for IRBs to address these 
concerns. IRB processes and procedures will continue to 
evolve as recommended by various committees and 
workgroups (e.g., as reported in NRC & IOM, 2005; 
NRC, 2003; U.S. HHS, 1993). 


All human subjects research conducted or sponsored 
by NERL is subject to both the 40 CFR 26 requirements 
and procedures set forth in EPA Order 1000.17 Change 
Al ( www.epa.gov/oamrtpnc/forms/1000 17a.pdf ). The 
EPA order establishes as policy that all research will 
comply with the Common Rule and with the order. All 
human research studies must be reviewed and approved 
by the EPA HSRRO before the work can begin. 

In NERL, the director of the division conducting or 
funding the research is the manager with the primary 
responsibility for developing the human subjects 
research protocol and for having that protocol reviewed 
by an independent IRB acceptable to the EPA HSRRO. 
The protocol also will be reviewed by the NERL 
HSRRO and by the appropriate NERL associate director 
before it is submitted to the IRB. Under 40 CFR 26.109, 
the IRB can demand changes to the research protocol 
and is the final authority for approving or disapproving 
the research activity. 

2.5.5 Internal EPA Review of Scientific and 
Ethical Issues 

After IRB approval is obtained, the division director 
will be the primary manager responsible for preparing a 
request for review and approval or exemption of the 
human subjects research by the EPA HSRRO. The 
division director will ensure that the request is consistent 
with EPA Order 1000.17 Al and all other policies or 
procedures that the EPA HSRRO may have established. 
The EPA HSRRO shall be the final authority for 
approving or disapproving the research effort. The EPA 
HSRRO may request additional reviews or establish 
additional policies and procedures for seeking review 
and approval. No human subjects research will 
begin—not even recruiting of potential 

participants—until the EPA HSRRO has approved or 
exempted the research. 

2.6 Informed Consent 

Informed consent is discussed extensively in 
Section 5 of this document. The major focus is that 
informed consent is a process, not a form, that “should 
be an on-going, interactive dialogue between research 
staff and research participants involving the disclosure 
and exchange of relevant information, discussion of that 
information, and assessment of the individual’s 
understanding of the discussion” (Recommendation 4.1, 
IOM, 2002). These comments emphasize how important 
true two-way communication is to comprehension, the 
second pillar in the informed consent process. Informed 
consent is built on three “pillars:” (1) information; (2) 


29 




comprehension; and (3) voluntary participation, or 
“voluntariness” (U.S. DHEW, 1979). Informed consent 
requires “provision of information to subjects about the 
purpose of the research, its procedures, potential risks, 
benefits, and alternatives, so that the individual 
understands this information and can make a voluntary 
decision whether to enroll and continue to participate” 
(Emanuel et al., 2000). 

2.7 Ensuring That Participant Behaviors Are 
Not Changed Adversely Because of Being 
in the Study 

The goal of observational human exposure studies is 
to collect information on people’s exposures to 
chemicals in their real-world environment as they carry 
on their normal daily activities. Researchers who 
conduct these studies, however, recognize that 
participation in a study may affect behavior. This cannot 
always be avoided, as simply agreeing to participate in a 
study may impact the participant’s activities and 
schedules. For example, this occurs when technicians 
visit homes to collect samples or when participants are 
asked to collect samples (e.g., food, urine), or to 
complete surveys, activity logs, or questionnaires. These 
types of changes in behavior may or may not affect the 
outcome of the study. 

Some changes in behavior can affect the study 
outcome. The Hawthorne Effect is a well-recognized 
phenomenon. It is an effect on an outcome variable 
caused by the fact that the participants of the study know 
they are participating in the study. The Hawthorne Effect 
originally referred to the increase in worker productivity 
observed when a worker is singled out and made to feel 
important; the increased productivity was not related to 
the environmental factors that were being studied. The 
effect was described based on a series of industrial 
productivity studies from 1927 to 1932. Similarly, some 
changes in participant behaviors may change the 
observations, measurements, and conclusions from 
observational human exposure studies. For example, 
participants may do more cleaning in their home because 
they do not want the researchers to think they are poor 
housekeepers; this could affect the measurement of 
environmental concentrations in the home. In a study of 
chemicals from consumer products, participants may 
think that because the researchers are studying the 
products, the products must be harmful. Therefore, study 
participants may elect not to use the products during the 
study in the same manner as they would normally. 
Alternatively, prospective participants may choose to 
use more of the household product to qualify for the 


study. As a result, the participant’s exposure to the 
chemicals could be either more or less than “normal.” 

Any change in a participant’s behavior that is related 
to the research question being addressed in the study 
may impact the study results. Researchers should try to 
anticipate how a study may impact participant behaviors 
and ensure that the study design and implementation 
protocols do not cause changes in behavior that may 
cause harm to a participant during a study. A number of 
study elements with the potential to influence 
participants’ behavior are listed in Text Box 2-6. 


Text Box 2-6. Study Elements That 

Could Affect People’s Behavior 


Eligibility criteria 


Recruiting approach and materials 


Enrollment approach 


Payments 


Retention strategy 


Types of measurements made and data collected 


Protocols for data collection 


Protocols for visits to homes 


Interactions with participants 


Communications 


It is very difficult to predict in advance how these 
elements may be interpreted and acted on by the 
participants. Researchers may learn from the experiences 
of others, including the “lessons learned” from experts 
and their publications. They may wish to engage the 
community representatives (see Section 6) in a thorough 
discussion of the issue. Community-based focus groups 
or pilot studies also may demonstrate how the various 
elements of the study may have an unintended impact. 
Additionally, researchers can be very careful in the 
informed consent process (see Section 5.1), to ensure 
that participants not only know, but that they understand 
the facts of the study (Gilbert, 2006), and that they 
comprehend that the goal is to observe and measure the 
participant’s exposures during their normal, everyday 
activities. 

2.8 Criteria and Standards for Monitoring 
Scientific and Ethical Issues 

Ethical requirements do not end when the 
participants sign the consent form and agree to 
participate. Indeed, as was stated above, informed 
consent is a process, not a form, and the process is an 
on-going dialogue between participants and researchers 
that continues throughout the study and beyond. In 
discussing respect for both potential and enrolled 


30 










subjects, Emmanuel et al. (2000) identify five actions 
that demonstrate respect for subjects, including 

(1) permitting withdrawal from the research, 

(2) protecting privacy through confidentiality, 

(3) informing subjects of newly discovered risks or 

benefits, 

(4) informing subjects of results of other relevant 

research, and 

(5) maintaining welfare of subjects. 

The authors conclude that these requirements can be 
met by diligent exercise of data and safety monitoring 
and oversight of the research effort. (Data and safety 
monitoring and oversight also are discussed throughout 
Section 4, but especially in Section 4.5 entitled “Data 
and Safety Monitoring and Oversight” and in 
Section 7.8, “Reporting Unanticipated Results and 
Observations.” The reader also is referred to those 
sections.) 

Creation of data and safety monitoring and oversight 
organization and procedures, combined with careful 
consideration of actions to ensure the ethical protection 
of participants, is perhaps the most important aspect of 
planning and implementing an observational human 
subjects study. The monitoring must include both the 
technical aspects of the study—like planning for actions 
if unsafe environmental conditions are observed—and 
also the ethical aspects of the study, such as those items 
listed above. The team of people involved in data and 
safety monitoring and oversight have to establish and 
implement mechanisms to get feedback on a continuing 
basis from the participants, in addition to monitoring and 
reviewing the scientific data. 

CIOMS recommends that all human subjects 
research protocols contain “A description of the plans 
for statistical analysis of the study, including plans for 
interim analyses, if any, and criteria for prematurely 
terminating the study as a whole if necessary” 
(Appendix A, CIOMS, 2002). To be consistent with this 
recommendation, the research team will need to develop 
and implement an approach for monitoring the scientific 
and ethical issues during the study, so that changes can 
be made to the study, or the study can be stopped if 
necessary. Criteria and standards need to be established 
against which study activities and results can be 
evaluated, and these criteria and standards need to be 
incorporated into the study design, the human subjects 
research protocol, and the QAPP. 

In developing an approach to monitor scientific and 
ethical issues during the study, the research team may 
choose to 

• identify the individual, team, advisory committee, or 


data safety monitoring board (DSMB) responsible for 
monitoring the progress and results of the study; 

• develop roles and responsibilities; 

• develop a schedule and timeline for the activities to be 
conducted; 

• develop goals for interim data analysis and prepare an 
analysis plan; 

• identify what data will be analyzed, how it will be 
processed and validated, and who will perform the 
analyses; 

• develop a plan for reporting interim results to the 
research team; 

• develop standards for reporting scientific and ethical 
issues to the research team; or 

• develop criteria for evaluating scientific and ethical 
issues that arise during the study. 

In a well-designed observational study for which the 
research team has adequately prepared, it is unlikely that 
there will be scientific issues requiring that the study be 
stopped. Nonetheless, it is important for criteria to be 
established for when the study needs to be changed or 
terminated. An example might be the participant 
retention rate. In a study with repeated measurements, a 
certain sample size is required to obtain statistically 
significant results. If the retention rate is poor, and too 
many participants drop out of the study, it may not be 
possible to meet the study objectives, and early 
termination of the study may be warranted (see Text 
Box 2-7 for issues that warrant early termination). 
However, it is anticipated that the study design would 
include contingency planning (for example, related to 
replacement). 

Developing criteria for study elements that may have 
associated ethical concerns as a study progresses will no 
doubt be more difficult than reviewing the measurement 
data. Nonetheless, assuring the ethical safety of the 
participants is critically important. There are no standard 
formulas for dealing with ethical concerns. For example, 
if the privacy of a number of study participants is 
compromised by a technician conducting the 
measurements in their homes, what criteria should be 
used to evaluate the severity of the issues? How many 
landlord-participant problems are too many before the 
study needs to be changed to exclude participants who 
rent their dwellings? Despite the challenges, the team of 
people involved in the data and safety monitoring and 
oversight effort should work diligently, with input from 
the community, to establish open and continuing 
channels of communication with participants, the 
community, and stakeholders - with the goal of ensuring 
that their involvement in the research effort is, and 


31 







remains to be, based on the three pillars of informed 
consent: (1) that the parties are fully informed of all of 
the relevant and useful information, (2) that the 
information is understood by the parties, and (3) that all 
parties continue to participate voluntarily. With diligent 
effort to continue an open dialogue with the involved 
parties - combined with thoughtful review and oversight 
of the technical study results and procedures - the 
monitoring and oversight team can ensure that 
participants are free to withdraw from the research at any 
time; are fully informed about the technical study 
results; understand any new information about relevant 
risks and benefits; and that the privacy and 
confidentiality of the subjects is properly protected. 
Through these efforts, the monitoring and oversight team 
will ensure that the welfare of the research subjects 
remains a focus of the study effort. 


Text Box 2-7. Examples of Issues That May Cause a 
Study To Be Stopped Early 

• Participant recruiting and enrollment—low response rates, 
disproportionate enrollment of select groups, problems 
associated with advertising, inadequate selection criteria 

• Informed consent—difficulties with the process and materials, 
poor comprehension 

• Participation—poor response to questionnaires, poor 
compliance with researcher requests in data collection 
activities 

• Burden—higher than predicted 

• Changes in participant behaviors—potential changes because 
of participation in the study 

• Grievances—participant issues 

• Retention—high dropout rates 

• Community issues—poor interactions, lack of support 

• Third-party issues—problems with landlords, spouses, or 
others 

• Collateral observations—identification of nonstudy hazards, 
difficulty reporting 

• Unanticipated results—high contaminant concentrations 
measured, unexpected results 

• New data indicating that participation in the study (or 
observations measured in the study) represent a risk to 
participants or others 


References 

Castelloe, JM (2000). Sample size computations and power 
analysis with the SAS system. Paper 265-25 in Proceedings 
of the 25 th Annual SAS Users Group International 
Conference. Cary, NC: SAS Institute, Inc. Available: 
http://support.sas.com/md/app/papers/powersamplesize.pdf 

[accessed 16 April 2008]. 

CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I 
Environmental Protection Agency Part 26 Protection of 


Human Subjects. U.S. Code of Federal Regulations. 
Available: http://www.access.gpo.gov/nara/cfr/waisidx 06/ 
40cfr26 06.html [accessed 12 June 2007], 

CIOMS (The Council for International Organizations of 
Medical Sciences) (2002). International Ethical Guidelines 
for Biomedical Research Involving Human Subjects. 
Geneva, Switzerland: CIOMS. Available at 
http://www.cioms.ch/frame guidelines nov 2002.htm 

[accessed 12 June 2007], 

Coggon D, Rose G, Barker DJP (1997). Epidemiology for the 
Uninitiated, Fourth Edition. London: BMJ Publishing 
Group Ltd. Available at 

http://www.bmi.com/epidem/epid.html [accessed 29 
January 2008]. 

Cohen Hubal EA, Sheldon LS, Zufall, MJ, Burke JM, Thomas 
KW (2000). The challenge of assessing children’s 
residential exposure to pesticides. Journal of Exposure 
Analysis and Environmental Epidemiology 10(6 part 2): 
638-649. 

Dallal, GE (2001). Some aspects of study design. In The Little 
Handbook of Statistical Practice at 
www.StatisticalPractice.com, and at 
http://www.tufts.edu/~gdallal/STUDY.HTM [accessed 29 
January 2008] 

Emanuel EJ, Wendler D, Grady C (2000). What Makes 
Clinical Research Ethical? JAMA 283(20): 2701-271 1. 

Gilbert, SG (2006). Supplementing the traditional institutional 
review board with an environmental health and community 
review board. Environmental Health Perspectives 114(10): 
1626-1629. 

Kraemer HC, Thiemann S (1987). How Many Subjects? 
Statistical Power Analysis in Research. Newbury Park, CA: 
Sage Publications. 

Lenth RV (2001). Some practical guidelines for effective 
sample size determination. American Statistician 55(3): 
187-193. Available: 

http://www.stat.uiowa.edu/techrep/tr303.pdf [accessed 13 
June 2007], 

NRC (National Research Council) (2003). Protecting 
Participants and Facilitating Social and Behavioral 
Sciences Research. Washington, DC: The National 
Academies Press. Available: 
http://books.nap.edu/catalog.php7record id= 10638 

[accessed 12 June 2007], 

NRC & IOM (National Research Council and Institute of 
Medicine) (2005). Ethical Considerations for Research on 
Housing-Related Health Hazards Involving Children. 
Washington, DC: The National Academies Press. Available: 


32 











http://books.nap.edu/catalog.php7record id=l 1450 

[accessed 12 June 2007]. 

OHRP (Office for Human Research Protections) (2007). U.S. 
Department of Health and Human Services [Online], 
Available: http://www.hhs.gov/ohrp/ [accessed 13 June 
2007], 

Resnik DB, Wing S (2007). Lessons learned from the 
Children's Environmental Exposure Research Study. Am J 
Public Health 97(3): 414-8. 

U.S. DHEW (U.S. Department of Health, Education, and 
Welfare) (1979). The Belmont Report: Ethical Principles 
and Guidelines for the Protection of Human Subjects of 
Research. Washington, D.C.: National Commission for the 
Protection of Human Subjects of Biomedical and 
Behavioral Research. Available: 

http://ohsr.od.nih.gov/guidelines/belmont.html [accessed 
June 2007], 


U.S. EPA (U.S. Environmental Protection Agency) (2000). 
Comments on the use of data from the testing of human 
subjects: A report by the Science Advisory Board and the 
FIFRA Scientific Advisory Panel. Environmental Protection 
Agency, Science Advisory Board. EPA-SAB-EC-00-017. 
Available: 

http://www.epa.gOv/scipolv/sap/meetings/1999/november/e 

cOO 17.pdf Taccessed 16 April 2008], 

U.S. HHS (U.S. Department of Health and Human Services) 
(1993). Protecting Human Research Subjects: Institutional 
Review Board Guidebook. Office for Human Research 
Protections. Available: 

http://www.hhs.gov/ohrp/irb/irb guidebook.htm [accessed 
12 June 2007], 

Van Belle G, Fisher L (2004). Biostatistics: A Methodology 
for the Health Sciences (2 nd Edition) Hoboken, NJ: John 
Wiley & Sons. 

Wackerly DD, Mendenhall W, Scheaffer RL (2001). 
Mathematical Statistics with Applications (6 lh Edition). 
Pacific Grove, CA: Duxbury Press. 


33 


















SECTION 3 


Ensuring Protection of Vulnerable Groups 


Concern for the protection of vulnerable groups is 
fundamental to modem ethical thought and guidelines. 
The Belmont Report was “meant to provide broad 
principles that could be used to generate specific rules 
and regulations in response to [U.S.] research scandals 
such as Tuskegee and Willowbrook. 11 It focuses on 
informed consent, favorable risk-benefit ratio, and the 
need to ensure that vulnerable populations are not 
targeted for risky> research ” [emphasis added] (Emanuel 
et al., 2000). 

The Common Rule requires IRBs to assure that 
“additional safeguards have been included in the study to 
protect the rights and welfare of these [vulnerable] 
subjects” [at 40 CFR 26.111(b) in CFR, 2006a], If an 
observational human exposure study includes vulnerable 
research participants, it is essential that the investigators 
be cognizant of the special issues and requirements of 
research involving vulnerable populations. Researchers 
have to justify the involvement of vulnerable 
populations in the research study and include the 
appropriate safeguards for protection of their safety and 
welfare. The Common Rule protections are discussed 
further in the IRB guidebook (U.S. HHS, 1993). EPA 
regulations include not only the general protections for 
vulnerable populations found in the Common Rule 
(Subpart A) but also define additional protections for 
children and for pregnant or nursing women (and their 
fetus or nursing child) in Subparts B, C, and D (CFR, 
2006a). 

The section begins by identifying or defining 
vulnerable groups and then discusses ethical issues that 


11 For more information about these and other research scandals, see Ethical 
and Policy Issues in Research Involving Human Participants, Vol. /, Report 
and Recommendations of the National Bioethics Advisory Commission, 
Bethesda, MD, August, 2001. See p. 153 for information about the 
Willowbrook State School experiments. The report is available at 
www.bioethics.gov/reports/past commissions/nbac human part.pdf 

(Accessed September 3, 2007). 


may be important in conducting observational human 
exposure studies involving those groups, especially 
children and pregnant women. The discussions about the 
ethical issues are based largely on EPA’s human subjects 
regulations and on the recommendations from the 
Council for International Organizations of Medical 
Sciences document, International Ethical Guidelines for 
Biomedical Research Involving Human Subjects 
(CIOMS, 2002). 

3.1 Identification of Vulnerable Groups 

In the United States, human subjects regulations 
(45 CFR 46 and 40 CFR 26) do not formally define 
vulnerable populations. Instead, the Common Rule gives 
examples of potentially vulnerable groups (see Text Box 
3-1). In addition, HHS extends added human subjects 
protections to pregnant women, human fetuses, 
neonates, prisoners, and children as vulnerable groups 
(45 CFR 46, Subparts B, C, and D, see CFR, 2006b). 
Analogous but somewhat more stringent protections for 
children, pregnant or nursing women, and fetuses are 
specified in Subparts B, C, and D of the EPA Rule (40 
CFR 26). The regulations do not preclude other groups 
from being considered vulnerable, however, and the 
National Institutes of Health (NIH), in its Human 
Participant Protections Education for Research Teams 
online tutorial (NIH, 2002), lists students or employees 
and terminally ill or comatose patients as potentially 
vulnerable groups. 

CIOMS defines vulnerable persons as those who are 
relatively (or absolutely) incapable of protecting their 
own interests. Vulnerability here refers to a substantial 
incapacity to protect one’s own interests owing to such 
impediments as lack of capability to give informed 
consent, lack of alternative means of obtaining medical 
care or other expensive necessities, or being a junior or 
subordinate member of a hierarchical group. Vulnerable 
persons may have insufficient power, intelligence, 
resources, strength, or needed attributes to protect their 


35 









own interests (CIOMS, 2002) (see Text Box 3-2). 
Because of their incapacity to protect their own interests, 
ethically perceptive researchers will plan and implement 
special provisions for the protection of the rights and 
welfare of the vulnerable persons. 


Text Box 3-1. Potentially Vulnerable Groups 
Identified in U.S. Regulations 

Common Rule: 

• Children 

Examples of vulnerable 

• Pregnant women (and their 

groups 

fetuses) 

(40 CFR 26) 

• Nursing women (and their 
neonates) 

• Prisoners 

• Handicapped persons 

• Mentally disabled persons 

• Economically disadvantaged 
persons 

• Educationally disadvantaged 
persons 

EPA extends stringent 

• Children 

protections to these 

• Pregnant women (and their 

groups 

fetuses) 

(40 CFR 26) 

• Nursing women (and their 
neonates 

HHS extends additional 

• Children 

protections to these 

• Pregnant women and fetuses 

groups 
(45 CFR 46) 

• Nursing women and neonates 

• Prisoners 

Additional vulnerable 

• The terminally ill 

groups in NIH training 
materials 

• Students and employees 

• Comatose patients 


Although Federal regulations define vulnerability in 
terms of the person’s ability to protect their own 
interests or particular sensitivity to risks because of 
physical condition, the lay public may perceive a broader 
definition of vulnerability as it relates to education, 
economics, social status, and other factors. As shown in 
Text Boxes 3-1 and 3-2 and described above, the 
concept of vulnerability is broader than that presented in 
the Common Rule. It is not adequate to simply check the 
list in Text Box 3-1 to identify if a potentially vulnerable 
group is included in an observational study. The 
researchers should assess the potential vulnerability of a 
study population within the study by evaluating the 
characteristics (e.g., socioeconomic status) of the study 
population within the context of the study by considering 
the various design elements of the study, as discussed in 
Section 2. 


Text Box 3-2. Potentially Vulnerable Groups 
Identified in International Guidance 

(Council for International Organizations of 
Medical Sciences, 2002) 

• Junior or subordinate members of a hierarchical group; 
examples include employees, students, members of the armed 
forces, police, and others who work for, or closely with re¬ 
searchers; they may have expectations of preferential 
treatment if they agree to participate or fear of disapproval or 
retaliation if they refuse to participate in a study. 

• Elderly persons, who may acquire attributes that define them 
as vulnerable with advancing age. 

• Residents of nursing homes. 

• People receiving welfare benefits or social assistance. 

• People with low or no incomes (poor and unemployed). 

• Homeless persons. 

• Nomads. 

• Refugees or displaced persons. 

• Some ethnic and racial minority groups. 

• People with incurable diseases (in clinical studies). 

• The politically powerless. 

• Members of communities unfamiliar with modern medical 
concepts (applies to clinical studies) 


3.2 Justification for Involving Vulnerable 
Persons in Observational Research 

The Common Rule requires IRBs to ensure that the 
selection of subjects is equitable [40 CFR 26.111(a)(3)] 
and instructs the IRB to consider the “purposes of the 
research and the setting in which the research will be 
conducted.” CIOMS goes further and recommends that 
“Special justification is required for inviting vulnerable 
individuals to serve as research subjects” (CIOMS, 
2002). 12 


12 

‘ In the commentary on Guideline 13 in CIOMS (2002), the committee states 
that the central problem presented by plans to involve vulnerable persons as 
research subjects is that such plans may entail an inequitable distribution of 
the burdens and benefits of research participation. Classes of individuals 
conventionally considered vulnerable are those with limited capacity or 
freedom to consent or to decline to consent. They are the subject of specific 
guidelines in the CIOMS document (Guidelines 14 and 15) and include 
children, and persons who, because of mental or behavioral disorders, are 
incapable of giving informed consent. Ethical justification of their 
involvement usually requires that 

• the research could not be carried out equally well with less vulnerable 
subjects; 

• the research is intended to obtain knowledge that will lead to improved 
diagnosis, prevention, or treatment of diseases or other health problems 
characteristic of, or unique to, the vulnerable class—either the actual 
subjects or other similarly situated members of the vulnerable class; 

• research subjects and other members of the vulnerable class from which 
subjects are recruited will ordinarily be assured reasonable access to any 
diagnostic, preventive, or therapeutic products that will become available 
as a consequence of the research; 

• the risks attached to interventions or procedures that do not hold out the 
prospect of direct health-related benefit will not exceed those associated 


36 











CIOMS recommendations, although written to 
address biomedical research, also generally are 
applicable to observational human exposure studies. The 
authors of this document consider the CIOMS 
requirement that the research could not be carried out 
equally well with less vulnerable subjects to be 
particularly important. EPA and NERL researchers 
should include vulnerable groups in observational 
human exposure studies only if their participation is 
critical to the success and applicability of the research. 
Even then, EPA and NERL researchers will have to meet 
stringent standards for protecting the rights and safety of 
the vulnerable participants. For example, EPA 
regulations governing observational research with 
children are even more stringent than the CIOMS 
guideline. If such research does not hold out the prospect 
of direct benefit to the child, no increase whatsoever 
over minimal risk is permitted. 

However, many observational human exposure 
studies are developed specifically to study the exposures 
of selected vulnerable groups to chemicals and other 
environmental stressors in everyday environments. So, 
researchers should be prepared to address the issues 
associated with vulnerable groups in observational 
research. Furthermore, as discussed in Section 3.4, there 
has been increased concern in recent years that exclusion 
of vulnerable groups from research studies is not ethical. 
Failure to conduct research with vulnerable groups may 
deprive them of the benefits of research. NIH, for 
example, has a policy (NIH, 1998) with a goal of 
increasing participation of children in research. 

3.3 Minimal Risk and Vulnerable Groups 

EPA has codified protections for children, pregnant 
or nursing women, and fetuses in Subparts B, C, and D 
of the EPA human subjects rule (40 CFR 26). Subpart B 
strictly prohibits research involving intentional exposure 
of children or pregnant or nursing women (and, 
therefore, exposure of her fetus). 

EPA’s regulations do allow for observational 
research involving fetuses and pregnant women (40 CFR 
26 Subpart C) or children (40 CFR 26 Subpart D) but 
with additional protections in place and with strict 
limitations on research that presents more than minimal 


with routine medical or psychological examination of such persons unless 
an ethical review committee authorizes a slight increase over this level of 
risk (Guideline 9); and, 

• when the prospective subjects are either incompetent or otherwise 
substantially unable to give informed consent, their agreement will be 
supplemented by the permission of their legal guardians or other 
appropriate representatives. 


risk (CFR, 2006a). 13 When considering vulnerable 
groups, The Institutional Review Board Guidebook (U.S. 
HHS, 1993) states that “IRBs should therefore determine 
whether the proposed subject population would be more 
sensitive or vulnerable to the risks posed by the research 
as a result of their general condition or disabilities. If so, 
the procedures would constitute more than minimal risk 
for those subjects.” 

When conducting observational human exposure 
studies, it is recommended that researchers consult these 
regulations and guidebooks. NERL researchers also will 
need to ensure that all of the requirements in Subparts B, 
C, and D of the EPA Human Subjects Rule are met. 

3.4 Research Involving Children 

Children long have been recognized as a vulnerable 
group in research studies. EPA and HHS both extend 
special protections to children (CFR, 2006a,b). There are 
many books, reports, and research manuscripts that 
specifically address issues associated with research 
involving children (e.g., NRC & IOM, 2005; IOM, 
2004; Kodish, 2005; NRC, 2003; AAP, 2003). 

CIOMS has drafted guidelines for including children 
in biomedical research (Guideline 14, CIOMS, 2002). 
The guidelines require an investigator to provide the 
assurances shown in Text Box 3-3 before undertaking 
research involving children. 


Text Box 3-3. Assurances Required by CIOMS Before 
Research Involving Children May Begin 

• the research might not equally well be carried out with adults; 

• the purpose of the research is to obtain knowledge relevant to 
the health needs of children; 

• a parent or legal representative of each child has given 
permission; 

• the agreement (assent) of each child has been obtained to the 
extent of the child’s capabilities; and 

• a child’s refusal to participate or continue in the research will be 
respected. 


The participation of children in some observational 
human exposure studies is critical to characterizing 
children’s exposures to chemicals in the environment. It 
is well recognized that children are not “little adults,” 
and that their exposures to chemicals differ (and, in 


13 Minimal risk is defined at 40 CFR 26.102(i) and again at 40 CFR 
26.402(g). It “means that the probability and magnitude of harm or discomfort 
anticipated in the research are not greater in and of themselves than those 
ordinarily encountered in daily life or during the performance of routine 
physical or psychological examinations or tests.” 




37 













some cases, are higher) from those of adults. Children 
are behaviorally and physiologically different from 
adults. Their interaction with their environment, through 
activities such as playing on floors, mouthing of hands 
and objects, and handling of food, may increase contact 
with contaminated surfaces. Children have 
proportionately higher breathing rates, relative surface 
area, and food intake requirements that also may 
increase exposure. Differences in absorption, 
metabolism, storage, and excretion may result in higher 
biologically effective doses to target tissues. Immature 
organ systems may be more susceptible to toxicological 
challenges. Windows of vulnerability, when specific 
toxicants may permanently alter the function of an organ 
system, are thought to exist at various stages of 
development. Because the factors influencing children's 
exposures to chemicals are not characterized well 
(Cohen Hubal et al., 2000), it is sometimes important 
that observational human exposure studies involve 
children. 

Because children are so vulnerable, there long has 
been concern about including them in research studies, 
and biomedical research often excluded children. 
However, in recent years, there has been concern that 
excluding children from research is not ethical. NIH's 
Policy and Guidelines on the Inclusion of Children as 
Participants in Research Involving Human Subjects 
(NIH, 1998) has a goal of increasing participation of 
children in research. The policy of NIH is that children 
must be included in all human subjects research 
conducted or supported by NIH, unless there are 
scientific and ethical reasons not to include them. 
Proposals or applications to NIH for research have to 
present an acceptable justification if children will be 
excluded from a research study. Of course, as discussed 
above, if the research topic is irrelevant to children, the 
CIOMS guidelines would recommend that they be 
excluded from the research. 

Observational human exposure studies conducted by 
NERL are not expected to involve greater than minimal 
risk. It will be the responsibility of the NERL 
researchers to present adequate information for the IRB 
to demonstrate that the research does not involve greater 
than minimal risk. Researchers designing observational 
research studies should carefully evaluate the risks and 
benefits specific to their study and the participants 
involved. In developing the study design and human 
subjects protocols, researchers need to ensure that the 
protocols ensure the protection of the rights and welfare 
of the participant children, and that risks and harm are 
minimized. The perception of risks and benefits, both by 


the individual and by the family or community, may 
influence the risk-benefit determination. It may prove 
useful for the research team to consult with other 
experienced researchers who have conducted similar 
studies and with members of the IRB to ensure that the 
information included in the human subjects research 
protocol is adequate for the IRB’s review. 

It is recommended that researchers consider all of 
the potential issues associated with involvement of 
children in their studies in developing the study design 
and research protocols, including the role of the family. 
EPA’s human subjects rule for observational research 
not involving greater than minimal risk to children (40 
CFR 26.404) (i.e., the kinds of observational human 
exposure studies that NERL exposure research is likely 
to entail) focuses on obtaining assent of the children and 
permission of their parents or guardians. But the role of 
the family goes far beyond their involvement in the 
informed consent process. In observational human 
exposure studies, even when children are the 
participants, the parents or guardian play a key role in 
the collection of data and information during the study. 
For studies with very young children, family members 
supply all of the information relevant to the child. NERL 
researchers need to ensure that both the child and the 
parents or guardians and other caregivers are informed 
fully and are willing participants. Without their willing 
participation, the research cannot be successful. 

3.5 Women as Research Subjects 

Women are routinely included as research 
participants in observational human exposure studies. 
However, pregnant women and their fetuses are 
vulnerable groups and require special protections. EPA’s 
human subjects rule prohibits intentional dosing studies 
and provides additional controls for observational 
research (40 CFR 26, Subparts B and C). 

CIOMS (2002) includes two guidelines for 
biomedical research involving women as research 
subjects. The first of these, number 16, states that 
women should not be excluded from biomedical 
research because of the potential for becoming pregnant 
during a study. The document continues, “A general 
policy of excluding from such clinical trials women 
biologically capable of becoming pregnant is unjust in 
that it deprives women as a class of persons of the 
benefits of new knowledge derived from the trials.” The 
second relevant CIOMS guideline, number 17, asserts 
that, if involved in a research study, pregnant women 
should be fully informed, and included only if the 


38 


research benefits pregnant women and is thoroughly 
supported by reliable evidence in animal studies. 

Although the CIOMS guideline specifically 
addresses biomedical research, the ethical concepts 
behind the guidelines generally may be applicable to 
observational human exposure studies. EPA’s human 
subjects rule is completely consistent with the HHS rule 
in adding additional protections for pregnant women and 
fetuses involved in observational research (40 CFR 
26.304 and 45 CFR 46.204). These additional 
protections (specified in 45 CFR 46.204 subparagraphs a 
through j) reflect the CIOMS recommendations by 
requiring: availability of data from previously conducted 
studies to assess the risk to pregnant women and fetuses; 
scientific necessity for inclusion of pregnant women and 
fetuses (i.e., providing benefit to the woman or fetus, or 
producing important, but otherwise unobtainable, 
biomedical knowledge); that risk is reduced to the least 
possible level for achieving the objectives of the 
research; and other protections. 

3.6 Other Potentially Vulnerable Groups 

HHS specifies additional protections for prisoners as 
a potentially vulnerable group in Subpart C of 45 CFR 
26. Additional requirements for other vulnerable groups 
in research studies are not specifically defined in either 
EPA’s or HHS’ human subjects rules. Nonetheless, other 
groups (as discussed in Section 3.1) may be considered 
to be vulnerable and, as such, may warrant additional 
consideration and protection as required in the Common 
Rule. For these other potentially vulnerable groups, such 
as employees, students, handicapped persons, mentally 
disabled persons, and economically or educationally 
disadvantaged persons, nursing home residents or 
otherwise incapacitated elderly, etc., the Common Rule 
requires researchers and IRBs to fully evaluate the 
protocols to ensure that the safety and welfare of the 
groups will be protected. As discussed in Section 3.1, It 
also should be noted that, although Federal regulations 
define vulnerability in terms of the ability to protect 
one’s own interests, the lay public may perceive a 
broader definition of vulnerability as it relates to 
education, economics, social status, and other factors. 
The researcher should evaluate vulnerability in this 
broader context to ensure that adequate safeguards are 
included for potentially vulnerable populations that do 
not meet the definition of the Federal regulations. 


References 

AAP (American Academy of Pediatrics) (2003). Pediatric 
Environmental Health. (2 nd Edition). Elk Grove Village, IL: 
American Academy of Pediatrics. 

CFR (Code of Federal Regulations) (2006a). 40 CFR Chapter 
I Environmental Protection Agency Part 26 Protection of 
Human Subjects. U.S. Code of Federal Regulations. 
Available: 

http://www.access.gpo.gov/nara/cfr/waisidx 06/40cfr26 06. 

html [accessed 12 June 2007], 

CFR (Code of Federal Regulations) (2006b). 45 CFR Subtitle 
A Department of Health and Human Services Part 46 
Protection of Human Subjects. U.S. Code of Federal 
Regulations. Available: 

http://www.access.gpo.gov/nara/cfr/waisidx 06/45cfr46 06.ht 

ml [accessed 13 June 2007], 

CIOMS (The Council for International Organizations of 
Medical Sciences) (2002). International Ethical Guidelines 
for Biomedical Research Involving Human Subjects. 

Geneva, Switzerland: CIOMS. Available at 
http://www.cioms.ch/frame guidelines nov 2002.htm 

[accessed 12 June 2007]. 

Cohen Hubal EA, Sheldon LS, Burke JM, McCurdy TR, Berry 
MR, Rigas ML, Zartarian VG, Freeman NCG (2000). 
Children’s exposure assessment: a review of factors 
influencing children’s exposure, and the data available to 
characterize and assess that exposure. Environ Health 
Perspect 108(6): 475-486. 

Emanuel EJ, Wendler D, Grady C (2000). What makes 
clinical research ethical? JAMA 283(20): 2701-2711. 

IOM (Institute of Medicine) (2004). Ethical Conduct of 
Clinical Research Involving Children. Washington, DC: 

The National Academies Press. Available: 
http://www.nap.edu/catalog.php7record id= 10958 [accessed 
16 April 2008], 

Kodish E (Ed.) (2005). Ethics and Research with Children: A 
Case-Based Approach. New York: Oxford University Press. 

NBAC (National Bioethics Advisory Commission) (2001). 
Ethical and Policy Issues in Research Involving Human 
Participants, Volume I: Report and Recommendations of the 
National Bioethics Advisory Commission. Bethesda, MD: 
National Bioethics Advisory Commission. Available: 
http://www.bioethics.gov/reports/past commissions/nbac h 

uman part.pdf [accessed 3 September 2007]. 


39 












NIH (National Institutes of Health) (2002) Human Participant 
Protections Education for Research Teams [online tutorial]. 

NIH (National Institutes of Health) (1998). NIH Policy and 
Guidelines on The Inclusion of Children as Participants in 
Research Involving Human Subjects. Available: 
http://grants.nih.gov/grants/guide/notice-files/not98- 

024.html [accessed 13 June 2007], 

NRC (National Research Council) (2003). Protecting 
Participants and Facilitating Social and Behavioral 
Sciences Research. Washington, DC: The National 
Academies Press. Available: 
http://books.nap.edu/catalog.php7record id= 10638 

[accessed 12 June 2007], 


NRC & IOM (National Research Council and Institute of 
Medicine) (2005). Ethical Considerations for Research on 
Housing-Related Health Hazards Involving Children. 
Washington, DC: The National Academies Press. Available 
http://books.nap.edu/catalog.php7record id=l 1450 

[accessed 12 June 2007]. 

U.S. HHS (U.S. Department of Health and Human Services) 
(1993). Protecting Human Research Subjects: Institutional 
Review Board Guidebook. Office for Human Research 
Protections. Available: 

http://www.hhs.gov/ohrp/irb/irb guidebook.htm [accessed 
12 June 2007], 


40 







SECTION 4 


Privacy, Confidentiality, and Other Concerns Related 
to Observational Human Exposure Studies 


Observational human exposure studies are designed 
to describe people’s contact with pollutants as they go 
about their everyday lives. Of necessity then, these 
studies take place in the locations that participants often 
consider to be personal and private. Clinical research 
studies generally are conducted in a research facility, a 
clinic, a hospital, or some other institutional or medical 
setting. Survey research may be conducted by mail, over 
the phone, or in another “neutral” setting. But, 
observational human exposure studies are conducted in 
the participants’ “personal” environment—their home, 
daycare center, school, vehicle, workplace, or other 
environments that people occupy during their routine 
daily activities. This difference in the research setting 
means that researchers involved in observational human 
exposure studies have an even greater challenge in 
meeting the ethical obligation to respect the privacy of 
the participants. 

When exposure science researchers like those at 
NERL enter a home to carry out their studies, the 
“expectations and constraints may be strikingly different 

i than when research is carried out in a medical setting” 
(p. 64, NRC & IOM, 2005). The legal precept of 
freedom from unreasonable search and seizure and the 
historic and deeply rooted principle that “a man’s home 
is his castle” contribute to a belief in the “sanctity of the 
home” (see the discussion on pp. 62-66, NRC & IOM, 
2005). 

The joint NRC and IOM report Ethical 
Considerations for Research on Housing-Related Health 
Hazards Involving Children discusses the ethical issues 
associated with entering a participant’s home to conduct 
research and explores the researchers’ responsibilities 
that derive from conducting research in people’s homes 
(NRC & IOM, 2005). These housing-related discussions 
are particularly relevant to observational human 
exposure studies, which often include environmental and 


biological measurements in people’s homes or personal 
locations. Many of the topics identified in that report are 
discussed in this section (Text Box 4-1). 


Text Box 4-1. Topics in Section 4 

Privacy Issues 
Confidentiality 

Confidentiality of Information 
Confidentiality of Participation 
Collateral Observations 

Potential Nonstudy Hazards in the Residence 
Collateral Observations with Mandated Reporting 
Requirements 

Hazard Communication 
Planning and Staff Training 
Third-Party Issues 

Determining Whether a Third Party is a Human Subject 
Informing Third Parties of Research Activities 
Research Results and Third Parties 
Data and Safety Monitoring and Oversight 


4.1 Privacy Issues 

Privacy refers to an expectation that a person is free 
from intrusion into personal matters and is free from the 
presence or view of others. The Institutional Review' 
Board Guidebook defines privacy as “control over the 
extent, timing, and circumstances of sharing oneself 
(physically, behaviorally, or intellectually) with others” 
(U.S. HHS, 1993). Beauchamp and Childress find that 
the right to privacy is based on the principle of respect 
for autonomy. “We often respect persons by respecting 
their autonomous wishes not to be observed, touched, or 
intruded upon.... A loss of privacy occurs if others use 
any of several forms of access, including intervening in 
zones of secrecy, anonymity, seclusion, or solitude” (pp. 
295-296, Beauchamp and Childress, 2001). 







Although research participants may agree to allow 
researchers to enter their home or other zone of personal 
space to conduct their research measurements, they have 
not abrogated their right to privacy. “When individuals 
voluntarily grant others some form of access to 
themselves, their act is an exercise of the right to 
privacy, not a waiver of that right” (p. 297, Beauchamp 
and Childress, 2001). Researchers should remember that 
they are guests in the homes for a specific purpose. 
“When people visit a home, there are social expectations 
about what is acceptable behavior. People who are 
invited into a home are expected to be sensitive to and 
respectful of the host’s customs and values” (p. 65, NRC 
& IOM, 2005). 

By their very nature, observational human exposure 
studies encroach on the privacy of a research participant. 
Entry in a participant’s home (or other personal zones) 
does represent a loss of privacy, but researchers should 
be careful to ensure that their presence does not become 
a violation of the individual’s right to privacy. The 
relationship between the researcher and the participant 
may be complicated, and there may be conflicts between 
the researcher’s role and their ethical obligations (NRC 
& IOM, 2005). In entering a participant’s personal 
space, it may be difficult, or impossible, to avoid making 
observations unrelated to the research question, thereby 
further intruding on the participant’s personal privacy. 
Indeed, there may be ethical and legal obligations for the 
researchers to respond to those observations. Beauchamp 
and Childress suggest that “policies carefully specify the 
conditions of access that will and will not count as a loss 
of privacy or a violation of the right to privacy. The 
policy should accurately define the zones that are 
considered private and not to be invaded, and should 
also identify interests that legitimately may be balanced 
against privacy interests” (Beauchamp and Childress, 
2001 ). 

Observational human exposure studies also may 
infringe on the privacy of other individuals, for example, 
other members of the participant’s family or household. 
Researchers should strive to minimize the intrusion and 
loss of privacy and to show respect for the privacy of 
study participants and third parties at all times (see Text 
Box 4-2 for a list of relevant privacy issues). It is 
incumbent on the researcher to recognize privacy issues 
in the design and implementation of the research study. 
The NRC & IOM report suggests that researchers 
anticipate the ethical issues that arise from conducting 
research in a person’s home, and that they take steps to 
correct them (1) by thinking through the issues as part of 
the study design; (2) by discussing the issues during the 


informed consent process; and (3) by ensuring that the 
frontline staff that enter a participant’s home 
“understand their role as members of the research team, 
how that role differs from the role of neighbor or friend, 
and how they should respond when they make 
observations that are not part of the protocol” (p. 66, 
NRC & IOM, 2005). 

Text Box 4-2. Privacy Issues 

• Researchers should develop an anticipatory plan for how to 
deal with privacy issues during the study. The plan should 
include a list of potential observations that could be of concern 
and a plan for how they will be handled. 

• The plan needs to address both the legal and ethical 
obligations of the researcher in response to situations where 
privacy is compromised. 

• Privacy issues will vary depending on the culture of the 
population being studied. What one individual or group may 
find as an invasion of privacy, another group may not have a 
concern about. 

• Privacy issues involve individual participants and may extend 
to third parties, including the community. 

• Researchers may find a meeting with community 
representatives to learn about the community residents and 
potential privacy issues to be helpful. Community 
representatives can help the researcher identify potential 
privacy issues and offer advice on how to address them. 

• Researchers may wish to respect the privacy of occupants 
sharing the study participant’s household or other study 
locations by providing advance notification of study visits and 
by giving them the opportunity not to be present during those 
visits. 

• Field staff should be trained on how to minimize breaches of 
privacy and how to handle privacy issues. 

• The informed consent process and form should address how 
the researcher will handle privacy issues such as collateral 
observations of household hazards 


4.2 Confidentiality 

Confidentiality and privacy are not the same thing. 
Confidentiality refers to limits on the dissemination of 
information disclosed by a person in a special 
professional relationship, such as the doctor-patient 
relationship or the participant-researcher relationship 
(Beauchamp and Childress, 2001). The Institutional 
Review Board Guidebook defines confidentiality as 
“pertains to the treatment of information that an 
individual has disclosed in a relationship of trust and 
with the expectation that it will not be divulged to others 
without permission in ways that are inconsistent with the 
understanding of the original disclosure” (U.S. HHS, 
1993). Emanuel et al. (2000) state that one way to 
respect the privacy of the participants is “by managing 
the information in accordance with confidentiality 


42 







rules.” Confidentiality in research also may extend to 
limiting dissemination of the knowledge that an 
individual is participating in a research study. 

As part of the research planning process, researchers 
are responsible for developing procedures to protect 
confidentiality and to define limits on the researcher’s 
ability to provide or protect confidentiality. Explaining 
plans or procedures for protecting confidentiality and 
their limits 14 to prospective research participants is an 
integral part of the informed consent process. 






4.2.1 Confidentiality of Information 

Many types of information may be collected in 
observational human exposure studies. Information may 
be collected through questionnaires, staff observations of 
residential or other environments, diaries, personal 
sample collection, environmental or residential sample 
collection, and collection of biological specimens. 
Measurement data from the collected samples become 
part of the information for a participant. The specific 
information to be obtained to address the research 
questions should be determined in the development of 
the study design and research protocol. 

Disclosure of information that can be linked to an 
individual may cause harm or distress to that individual. 
Researchers are responsible for developing safeguards to 
protect the confidentiality of information and physical 
samples collected from research participants (see, for 
example, Guideline 18, CIOMS, 2002). 15 

Researchers also should be aware that certain 
combinations of information from a study may 
sometimes lead to the indirect identification of the 
individual. Certain combinations of demographic 
information, for example, may make it relatively simple 


— 

14 Beauchamp and Childress (2001) discuss when one may be ethically 
justified in infringing on an individual’s privacy and confidentiality—for 
example, because of risks to others evidenced by biomarkers of infectious 
disease. They also discuss similar ethical issues that may arise in regard to 
genetic data. CIOMS (2002) Guideline 18 provides suggestions for 
safeguarding or disclosing genetic information. If exposure scientists 
collaborate with medical researchers or epidemiologists and obtain such 
information, they need to be cognizant of the relevant ethical issues and of the 
CIOMS guidelines. 

15 Guideline 18 states, “The investigator must establish secure safeguards of 
the confidentiality of subjects’ research data. Subjects should be told the 
limits, legal or other, to the investigators’ ability to safeguard confidentiality 
and the possible consequences of breaches of confidentiality.’’ Additional 
CIOMS commentary on the confidentiality guideline states, "Prospective 
subjects should be informed of limits to the ability of researchers to ensure 
strict confidentiality and of the foreseeable adverse social consequences of 
breaches of confidentiality. Some jurisdictions require the reporting to 
appropriate agencies of, for instance, certain communicable diseases or 
evidence of child abuse or neglect. . . . These and similar limits to the ability 
to maintain confidentiality should be anticipated and disclosed to prospective 
subjects.” 


to identify an individual. Precise geographic location 
information may be sufficient to pinpoint a residence. 
Researchers may use several strategies to reduce the 
likelihood of indirect identification when study results 
are reported (see, also. Text Box 4-3). 

• Redact from publications, reports, or public data sets 
information that might be used to indirectly identify a 
research participant. 

• Generalize exact information; for example, replace 
birth date with age or year of birth or classify age as 
part of a range. 

• Aggregate information across individuals; for 
example, only report data in cells of sufficient size to 
make individual linkages unlikely. 

• Reduce the specificity of geographic coordinate 
information to a level that a specific residence or other 
location can not be identified. 


Text Box 4-3. Approaches for Protecting 
Personally Identifiable Information 

• Developing procedures for safeguarding information prior to 
collecting the information 

• Ensuring that data or samples are anonymous by not 
collecting or by destroying identifying information or linkages 

• Restricting access to identifying information to only those 
requiring access 

• Assigning codes to participants, data, and samples rather than 
using identifiers 

• Physically separating identifying information and linkage files 
from other study information 

• Securing identifying information in locked files with limited 
access 

• Restricting identifying information from computers that are 
networked with other computers or electronic systems 

• Restricting identifying information from computers that are not 
kept in secure locations with limited access 

• Training research staff members on human subject protection 
and on information security procedures 


Another step that can help protect confidentiality is 
to obtain a Certificate of Confidentiality. Certificates of 
Confidentiality are issued by NIH (2002) to protect 
identifiable research information from forced disclosure. 
They allow the investigator and others who have access 
to research records to refuse to disclose identifying 
information on research participants in any civil, 
criminal, administrative, legislative, or other proceeding, 
whether at the Federal, State, or local level. Certificates 
of Confidentiality may be granted for studies collecting 
information that, if disclosed, could have adverse 
consequences for subjects or damage their financial 
standing, employability, insurability, or reputation. By 
protecting researchers and institutions from being 






compelled to disclose information that would identify 
research subjects. Certificates of Confidentiality help 
achieve the research objectives and promote 
participation in studies by assuring confidentiality and 
privacy to participants. Any research project that collects 
sensitive, personally identifiable information and that 
has been approved by an IRB is eligible for a certificate. 
Identifying information is broadly defined as any item or 
combination of items in the research data that could lead 
directly or indirectly to the identification of a research 
subject. 

Federal funding is not a prerequisite for a certificate. 
A Certificate of Confidentiality does not diminish, 
however, the investigator’s need to protect the 
personally identifiable information as described above. 

4.2.2 Confidentiality of Participation 

In some types of research, the knowledge that a 
person is participating in a particular research study 
could, potentially, put the participant at risk for harm or 
distress. This topic is discussed in The Institutional 
Review Board Guidebook , with special emphasis on 
behavioral and social research that deals with sensitive 
topics (U.S. HHS, 1993). The guidebook describes the 
need for additional safeguards to protect and prevent 
disclosure of the identity of participants, including the 
use of Certificates of Confidentiality for sensitive 
matters. 

Observational human exposure studies often pose 
particular challenges with regard to limiting 
dissemination of the knowledge of an individual’s 
participation in the study. Visiting the research 
participant’s residence to collect samples or to make 
observations will necessitate informing other family 
members or occupants about the visit and study 
procedures. Research participants may be asked to wear 
personal monitors over time periods ranging from a day 
to a week or more. Wearing these devices in public 
places, schools, or workplaces may identify them as a 
study participant or generate questions regarding the 
activity. Field staff visits to the participant’s home or 
setting up outdoor sample collection devices around the 
home also might disclose their participation. And, in 
some cases, third parties outside of the home have to be 
asked for permission or be informed that monitoring 
activities are taking place. 

Researchers and IRBs should consider whether 
knowledge of an individual’s participation by others 
might create potential for harm or distress in an 
observational human exposure study. Such risks might 
be limited to possible discomfort in attracting unwanted 


attention; this may be particularly true for adolescents. 
However, in some cases, the potential risks could be 
greater, for example, in cases where participation could 
provoke an adverse reaction from a landlord or 
employer. Oftentimes study protocols can be structured 
to minimize these potential risks. Through the informed 
consent process, prospective participants should be made 
aware of the limits of the researcher’s ability to protect 
knowledge of their participation in the study and of the 
possible risks of disclosure. 

4.3 Collateral Observations 

In the course of conducting an observational human 
exposure study, research staff may observe potentially 
unsafe conditions or situations that are unrelated to the 
research study. Such “collateral observations” may 
involve physical hazards in the study participant’s 
residential environment or evidence of situations, such 
as child abuse, that have to be reported to proper 
authorities. In preparing for the research study, it is 
recommended that researchers carefully plan for possible 
collateral observations, including their identification, 
staff training, and hazard communication and reporting. 
This may be a major element in the data and safety 
monitoring and oversight for the study. The informed 
consent process should reflect procedures used to 
manage collateral observations. Potential participants 
should be informed of situations in which confidentiality 
might be breached, such as statutory requirements for 
reporting abuse or imminent harm to self or others. 

4.3.1 Potential Nonstudy Hazards in the 
Residence 

Research staff conducting observational human 
exposure studies often will spend time in and around 
study participant residences. In the course of visiting a 
residence or conducting study-related observations, 
research staff may observe potential hazards unrelated to 
the research being performed (see Text Box 4-4). Some 
hazards may be associated with the potential for physical 
injury, whereas others may be related to exposure to 
chemical or biological agents. Some situations may be 
potential hazards only for young children, whereas other 
conditions may present potential hazards for all residents 
or occupants. 

The NRC & IOM recommend that researchers 
should consider such foreseeable observations and 
potential hazards in advance, develop responses to the 
risks, and submit the proposed plans to the IRB for 
review to ensure that they are appropriate “in the context 
of the research and the affected community.” The NRC 


44 


& IOM also advise that field staff should be trained in 
how to assess and respond to such risks 
(Recommendations 7.3 and 7.4, NRC & IOM, 2005). 
For other behaviors and risks that have not been 
specifically identified in advance, procedures should be 
included in the data and safety monitoring and oversight 
provisions of the study design and research protocol to 
address these issues. The fundamental ethical principle 
of beneficence would motivate researchers who observe 
serious harms to take steps to try to prevent those harms, 
even for observations that are not directly related to the 
study. The steps that they may take can range from 
immediate action to prevent an imminent and serious 
danger to statutory reporting of observations (see 
Section 4.3.2) to reporting the observation to the data 
and safety monitoring and oversight authority for advice 
on how to respond (see Section 4.5). (The reader is also 
referred to pages 59-61 and 134-144 of the NRC & IOM 
[2005] report for a more thorough discussion of 
researchers’ responsibilities in such cases.) 


Text Box 4-4. Potential Hazards that Might Be 
Encountered in a Residential Environment 

• Unsecured firearm 

• Uncovered electrical outlets 

• Unprotected stairways 

• Missing child-protective cabinet latches 

• Lack of window guards 

• Missing or inoperable smoke alarm 

• Housing code violations 

• Chipping or flaking paint—potential for lead exposure in older 
homes 

• Malfunctioning or unvented combustion appliances—potential 
for carbon monoxide exposure 

• Unsecured poisons or other dangerous products 

• Excessive mold growth 


4.3.2 Collateral Observations with 
Mandated Reporting Requirements 

Some collateral observations may have statutory 
requirements for reporting to designated authorities. 
Examples of such observations include 

• observed child or elder abuse or evidence of such 
abuse or neglect, 

• statements or actions of intent to harm self or others, 
and 

• certain communicable diseases. 

Because different reporting statutes pertain in 
different states, it is necessary for researchers to learn 
and understand the applicable reporting requirements for 
the study location. In the case of abuse, it is also 


important to understand what actions or situations are 
considered abusive in a particular state. Although direct 
physical harm or violence might be obvious to a research 
staff member, there are other conditions of neglect that 
might be more difficult to recognize or to know when to 
report. 

Study participants should be made aware of statutory 
requirements for reporting collateral observations as part 
of the informed consent process. Researchers should 
include the reporting requirements in the informed 
consent form (discussed in Section 5) and should ensure 
that the study participant fully comprehends this 
information and the impact on their privacy and 
confidentiality. 

4.3.3 Hazard Communication 

It is difficult for researchers to determine when and 
how to communicate with study participants or third 
parties about collateral observations related to potential 
hazards. A hazard might present such an imminent threat 
to health or safety that staff would need to communicate 
immediately with the participant or take action to 
mitigate the threat. In some cases, such as instances of 
abuse with attendant statutory reporting requirements, it 
may be necessary to breach confidentiality. More often, 
however, a potential hazard identified as a result of 
collateral observation may not be an imminent threat or 
pose a potential risk that is situation dependent or is 
related to third parties. A number of considerations in 
hazard communication come into play regarding 
confidentiality, privacy, the ability of the researcher to 
provide accurate and effective information regarding the 
hazard and hazard mitigation, and the ability of the study 
participant or others to effectively mitigate the hazard 
without unintended adverse consequences. The National 
Academy of Sciences Committee on Ethical Issues in 
Housing-Related Health Hazard Research Involving 
Children, Youth, and Families discussed many of these 
issues in depth (NRC & IOM, 2005). 

Different communities, cultures, or demographic 
groups can have different risk perceptions, which may 
affect how collateral observations are assessed and 
reported from one study location to the next. The AAP 
Committee on Environmental Health has prepared 
information regarding perception, identification, and 
communication of environmental health risks (AAP, 
2003). Researchers likely will benefit from including 
community members on the research team in developing 
the study design and research protocol or from 
consultation with community boards regarding 
identification of hazards and hazard communication. 


45 










It is important that any advice that the researcher 
might provide to study participants regarding hazard 
mitigation should be carefully considered. 
Considerations in recommending an action may include 
whether the mitigation approach has been shown to be 
effective, whether the study participant can understand 
and effectively implement the action, and whether 
unintended adverse consequences might result from 
taking an action. In some cases, it may be reasonable to 
refer the participant to another organization that can 
provide expert advice or assistance. 

4.3.4 Planning and Staff Training 

As part of the study planning process and protocol 
development, it is important that researchers be 
cognizant of the kinds of collateral observations that 
might occur in the implementation of the study protocol 
and to develop plans as to how such observations would 
be handled. Researchers may choose to include a 
systematic approach in hazard identification, such as 
using a home-hazard checklist that becomes an ancillary 
part of the study protocol. Alternatively, collateral 
observations could be handled on a case-by-case basis. 

Staff experience and training is a critical 
consideration for managing collateral observations. Staff 
members that visit study participant residences may not 
have expertise or experience in identifying many of the 
potential hazards without adequate training. All staff 
involved in a study, particularly those responsible for 
field data collection, should be trained on identification 
and reporting of collateral observations. This training 
should be study specific and likely will include, but not 
be limited to 

(1) identification of actions (e.g., child abuse) that have 
(state-specific) statutory reporting requirements, 

(2) conditions of neglect that may adversely impact 
study participants or third parties, 

(3) environmental hazards and situations that may be 
associated with imminent harm (e.g., combustible 
materials near an open flame, unsecured firearms 
accessible to very young children), 

(4) policies and procedures for reporting or intervention 
by members of the research team, and 

(5) local and state reporting requirements. 

It is advisable that this training be developed in 
consultation with community representatives who can 
provide input on potential hazards and situations that 
may be encountered in the study community, local 
norms and attitudes about potential interventions and 
reporting, and local agencies available to assist on these 
types of issues. It is also especially important to consider 


staff experience and training in hazard communication. 
Consistency in communication is very important, and 
researchers may decide to use materials prepared by 
other organizations that have expertise regarding a 
particular hazard. 

Another important element of planning for field data 
collection and training of research staff is on hazards and 
situations that the field staff may encounter during their 
field work. Although the previous discussion highlights 
the need to be prepared to report potentially negligent or 
illegal behaviors, these same behaviors may place the 
research staff in imminent danger during the conduct of 
their work in residences and communities. The research 
team should develop a plan for identifying potential 
situations, hazards, and dangers that may place the 
research team at risk of imminent harm. This should 
generally involve working with community 
representatives to identify the hazards and situations that 
may be of concern. For example, a researcher’s 
observation of illegal drugs in a study residence may 
place the researcher in potential danger. Similarly, if 
studies are conducted in areas with high crime rates, 
researchers need to be aware of the potential dangers and 
have a plan for addressing them. In some cases, 
situations may arise because of to inadvertent actions. 
For example, if an area has a high rate of daytime break- 
ins, the presence of researchers in the area may trigger 
calls to local authorities when the researchers, who are 
strangers, are observed in the neighborhood. Feedback 
from the community representatives should be solicited 
when developing a plan for responding to situations such 
as these. Comprehensive training should be developed 
for research field staff to assist them in identifying 
potentially dangerous situations and in responding to 
such situations. 

4.4 Third-Party Issues 

Third-party issues can arise in observational human 
exposure studies in two ways. First, the study may 
collect limited information about or related to 
individuals other than the study participants. Second, 
study activities may affect or involve people or 
organizations other than the study participants. 

Examples of activities that may involve or affect 
third parties in observational human exposure studies 
could include, but are not limited to the following types. 

• Asking the participant about demographic, 
occupational, smoking, or product use information for 
other household members 

• Collecting residential environmental samples in 
multiperson households 


46 


• Collecting environmental samples in common areas of 
multifamily housing units 

• Collecting personal or environmental samples in a day 
care, school, health care, or occupational setting 

• Measuring chemical occurrences or concentrations 
that may be of interest or import to other household 
members or to the community 

• Collecting activity or dietary information about a 
community 

It is important for researchers and research staff to 
understand whether and to what extent the research 
involves or affects third parties, and how third-party 
involvement might affect the study participants. Several 
examples of possible third-parties are listed in Text Box 
4-5. Study planning; IRB review; and communication 
before, during, and after the study should take third- 
party issues into account. 


Text Box 4-5. Possible Third-Parties in 
Exposure Studies 

• Household members not enrolled in the study 

• Relatives 

• Care givers for children or elders 

• School staff 

• Employers 

• Other members of the community 

• Building managers or facility operators 

• Landlords 


4.4.1 Determining Whether a Third Party 
Is a Human Subject 

It is up to the IRB to determine whether a third 
party is a human subject afforded human subject 
protections under the Common Rule. A third party 
would meet the Common Rule definition of a human 
subject [40 CFR 26.102(f)] if individually identifiable 
private information about them is collected (CFR, 2006). 
When this occurs, the informed consent of the third party 
must be obtained, or, if certain criteria are met, the IRB 
may determine that informed consent may be waived. It 
can be difficult to determine whether information about 
a third party is both individually identifiable and private. 
Discussions of this issue and recommendations for 
determining whether third-party information is 
identifiable and private have been submitted to the HHS 
Office of Human Research Protections by NIH (2001) 
and by the National Human Research Protections 
Advisory Committee (NHRPAC, 2002). 

Whether or not a third party is determined to be a 
human subject, the researcher should treat research 


information about a third party as confidential. 

4.4.2 Informing Third Parties of 
Research Activities 

Obtaining permission from or informing third parties 
of certain types of activities may be needed in some 
observational human exposure studies. For example, 
household members living with a study participant need 
to be informed about home study visits and residential 
sample collection activities. Study activities that occur 
outside of the participant’s home or yard may require 
informing or gaining permission from third parties. A 
study may include collection of environmental samples 
(i.e., ambient air, dust, soil) from outdoor common areas 
of multifamily housing where the study participant lives. 
Issues regarding privacy, permission, and payments for 
third parties in housing-related studies have been 
discussed in the NRC & IOM (2005) report. 

Observational human exposure studies also may 
include cases when study participants are asked to 
collect personal samples (i.e., wearing a personal air 
monitor) over a time period that includes time they 
spend in a school, day care, or workplace. Such 
monitoring might require informing or gaining 
permission from an organization’s staff or an employer. 
In each case, the researcher and IRB have to consider 
whether obtaining permission from or informing a third 
party is appropriate and, if so, to define the procedures 
for doing so. The researcher and IRB have to also 
consider the potential impact of third-party knowledge 
of research activities on confidentiality and risk for the 
study participant and have to ensure that it is clearly and 
fully explained in the informed consent process. 

4.4.3 Research Results and Third Parties 

Prior to initiating a research study, researchers 
should consider whether research results may be 
provided to third parties. In some studies, there may be 
reasons to inform household members living with a 
study participant about specific residential measurement 
results. In community research studies, aggregated or 
summary research results may provide a benefit to the 
community. In this case, it would be beneficial to seek 
out the advice of community representatives regarding 
results reporting prior to the study. Researchers also 
should determine whether there are State or local 
reporting requirements for some types of measurement 
results above specified action levels (i.e., blood-lead 
levels, heavy metal concentration in soil). It is important 
that the researcher and IRB ensure that confidentiality 
and privacy of study participants are carefully 


47 




considered in any case where reporting study results to 
third parties is contemplated or may be required. Ideally, 
the informed consent process would make clear whether, 
under what conditions, and how research results might 
be provided to third parties. 

4.5 Data and Safety Monitoring and 
Oversight 

The Common Rule requires for IRB approval that, 
“When appropriate, the research plan makes adequate 
provision for monitoring the data collected to ensure the 
safety of subjects.” [40 CFR 26.111(a)(6)]. 

Data and safety monitoring plans (DSMPs) are 
developed and applied in all clinical trial research 
studies. Clinical trials are prospective studies designed to 
answer specific questions about the effects or impact of 
particular biomedical or behavioral interventions. The 
DSMPs are used to insure the safety of participants, the 
validity of data, and appropriate termination of studies 
for which significant risks or benefits have been 
uncovered or when it appears that the trial cannot be 
concluded successfully (NIH, 1998; NCI, 2001; U.S. 
FDA, 2001). Depending on the study scope and potential 
risks and benefits, a data safety monitoring board 
(DSMB) may be created to assess procedures for data 
and safety monitoring and to independently assess safety 
and outcomes on an ongoing basis during the study. 

Formal independent monitoring boards or 
committees, like DSMBs, have not seen widespread use 
in observational human exposure studies, although much 
of the information included in DSMPs often has been 
captured in the research protocols. Researchers and IRBs 
may, however, consider using monitoring and oversight 
boards to help assure participant safety and research 
integrity in observational human exposure studies, 
particularly in complex longitudinal studies and in 
studies that include vulnerable subjects. 

At least two NIH institutes have developed 
guidelines for monitoring and oversight in the 
observational research that they sponsor. 

(1) The National Heart, Lung, and Blood Institute 
(NHLBI) has developed an interim policy on the 
creation and role of observational study monitoring 
boards (OSMBs) for observational research 
sponsored by that institute (NHLBI, 2007). OSMBs 
may be established for large or complex studies on a 
case-by-case basis. The role of the OSMB is “to help 
assure the integrity of the study by closely 
monitoring data acquisition for comprehensiveness, 
accuracy, and timeliness; and monitoring other 
concerns such as participant confidentiality.” 


(2) The National Eye Institute (NEI) has developed 
guidelines for data monitoring and oversight 
committees (DMOCs) for observational research 
(NEI, 2001). The role of the DMOC is to “assist the 
NEI and the study investigators in protecting the 
interests of study participants and in preserving the 
integrity and credibility of the study.” 

When appropriate, formal procedures for routine 
monitoring of scientific and ethical issues will need to be 
incorporated into observational research and approved 
by the IRB to ensure participant safety and the integrity 
of the research. Even though most observational human 
exposure studies are considered low-risk, there is often a 
need to detennine whether appropriate threshold values 
for biological or environmental levels of chemicals exist 
or can be determined that, if the threshold value is 
exceeded, it would trigger reporting or other actions. The 
safety of measurement procedures and equipment also 
has to be considered. Unanticipated adverse events also 
may be encountered in observational research. 
Participant consent and understanding of the research 
effort, participant recruitment, participant retention, and 
data accuracy and quality should all be monitored to 
ensure the scientific integrity of research results. 

The authors already have discussed (Section 2.8) the 
needs (1) to establish, in advance, criteria and standards 
for monitoring the research program in regard to both 
scientific and ethical issues; (2) to establish who will 
monitor and oversee the research progress (the 
monitoring and oversight authority, be it an individual, 
team, or review committee); and (3) to establish the 
roles, responsibilities, and authorities of the researchers 
and of the monitoring and oversight authority. The 
planning also should include steps to meet the IOM 
recommendations that researchers should “anticipate 
risks and behaviors that may be observed in the home... 
[and] develop anticipatory plans that specify how to 
assess and respond to risks when they are identified, and 
educate their staffs about the plan” (Recommendation 
7.3, p. 144. NRC & IOM, 2005). 

Once the procedures and organization for monitoring 
and oversight of the observational study are approved by 
the IRB, it is the responsibility of the researchers and of 
the monitoring and oversight authority to ensure that the 
planned actions are implemented. Implementation of the 
monitoring and oversight function may include the 
following items. 

• Ensuring that procedures for identifying, reporting, 
and responding to anticipated or unanticipated adverse 
events and safety issues are in place and are being 
followed 


48 


• Assessing and responding to risks when they are 
identified 

• Evaluating the performance and knowledge of the 
staff regarding identification of potential risks and the 
actions they should take 

• Implementing procedures for monitoring the informed 
consent process, participant behaviors, participant 
recruitment, participant retention, procedures to 
protect privacy and confidentiality, and other human 
requirements for adherence to the research protocol 
and compliance with ethical standards and with EPA’s 
human subjects rules 

• Ensuring that measurements and samples are collected 
as planned, and that data are reported on a timely basis 

• Evaluating whether the observed measurements 
exceed the pre-established threshold values and, if so, 
ensuring that reporting procedures and plans to 
respond to the potential risks are completed on a 
timely basis 

• Ensuring that quality assurance plans that define 
procedures for assessing and ensuring study protocol 
compliance are being met 

• Ensuring data quality targets are met through 
independent internal or external auditing requirements 

• Taking all warranted oversight actions to ensure the 
safety of the participants and the integrity of the study, 
including terminating the research study if appropriate 

References 

AAP (American Academy of Pediatrics Committee on 
Environmental Health) (2003). Pediatric Environmental 
Health. (2 nd Edition). Elk Grove Village, IL: American 
Academy of Pediatrics. 

Beauchamp TL, Childress JF (2001). Principles of Biomedical 
Ethics. (5 th Edition). New York, NY: Oxford University 
Press. 

CFR (Code of Federal Regulations) (2006). 40 CFR Chapter 
I—Environmental Protection Agency Part 26 Protection of 
Human Subjects. U.S. Code of Federal Regulations. 
Available: 

http://www.access.gpo.gov/nara/cfr/waisidx 06/40cfr26 06. 

html [accessed August 2007]. 

CIOMS (Council for International Organizations of Medical 
Sciences) (2002). International Ethical Guidelines for 
Biomedical Research Involving Human Subjects. World 
Health Organization. Geneva, Switzerland. Available: 
http://www.cioms.ch/frame guidelines nov 2002.htm 

[accessed June 2007], 

* 


Emanuel, EJ, Wendler D, Grady C (2000). What makes 
clinical research ethical? JAMA 283(20): 2701-271 1. 

NCI (National Cancer Institute) (2001). Essential Elements of 
a Data and Safety Monitoring Plan for Clinical Trials 
Funded by the National Cancer Institute. Available: 
http://www3.cancer.gov/rrp/dsm ess.html [accessed April 
2007], 

NEI (National Eye Institute) (2001). National Eye Institute 
Guidelines for Data Monitoring and Oversight of 
Observational Studies. Available: 

http://www.nei.nih.gov/funding/datastudies.asp [accessed 
April 2007]. 

NHLBI (National Heart Lung and Blood Institute) (2007). 
Monitoring Boards for Data and Safety (Interim Policy). 
Policy effective date: 14 May 2007. Available: 
http://public.nhlbi.nih. gov/ocr/home/GetPolicy.aspx?id=8 

[accessed September 2007], 

NHRPAC (National Human Research Protections Advisory 
Committee) (2002). Clarification of the status of third 
parties when referenced by human subjects in research. 
Available: 

http://www.hhs.gov/ohrp/nhrpac/documents/third.pdf 

[accessed April 2007], 

NIH (National Institutes of Health) (2002). Extramural 
Projects - Application Instructions (03/15/2002) - Detailed 
Application Instructions for Certificate of Confidentiality 
Involving Extramural Research Projects. Certificates of 
Confidentiality. Available: 

http://grants.nih.gov/grants/policy/coc/index.htm . [accessed 
April 2007] 

NIH (National Institutes of Health) (2001). Protection of third 
party information in research: Recommendations of the 
National Institutes of Health to the OJjice for Human 
Research Protections. Available: 
http://bioethics.od.nih.gov/nih third party rec.html 

[accessed March 2007]. 

NIH (National Institutes of Health) (1998). NIH Guide: NIH 
Policy for Data and Safety Monitoring. Available: 
http://grants.nih.gov/grants/guide/notice-files/not98- 

084.html [accessed April 2007]. 

NRC & IOM (National Research Council and Institute of 
Medicine) (2005). Ethical Considerations for Research on 
Housing-Related Health Hazards Involving Children. 
Washington, DC: The National Academies Press. Available: 
http://books.nap.edu/catalog.php7record id=l 1450 

[accessed June 2007]. 


49 

















U.S. FDA (U.S. Food and Drug Administration) (2001). Draft 
Guidance for Clinical Trial Sponsors on the Establishment 
of Clinical Trial Data Monitoring Committees. U.S. 
Department of Health and Human Services, Food and Drug 
Administration, Rockville, MD. Available: 
http://www.fda.gov/cber/gdlns/clindatmon.pdf . [accessed 
April 2007], 


U.S. HHS (U.S. Department of Health and Human Services) 
(1993). Protecting Human Research Subjects: Institutional 
Review Board Guidebook. Office for Human Research 
Protections. Available: 

http://www.hhs.gov/ohrp/irb/irb guidebook.htm [accessed 
June 2007], 


50 




SECTION 5 


Creating an Appropriate Relationship Between 


the Participant 


In observational human exposure studies, the 
researcher and the participant routinely interact with 
each other, often in the participant’s home or other 
private setting and often repeatedly over a number of 
days. The nature and setting of the interactions mean that 
exposure researchers should give special consideration 
to the many scientific and ethical issues that shape the 
relationship between participants and the researchers. In 
these studies, it is recommended that a strong 
relationship, built on openness and trust, should be 
developed between the researcher and participant. The 
nature of that relationship and the ethical principles 
underpinning an appropriate relationship are the focuses 
of this section of the document. 

This relationship should be established on the ethical 
values of respect for the participant’s autonomy and 
respect for their welfare. Emanuel and his co-authors 
find that these two ethical values translate into specific 
responsibilities for an ethical researcher in regard to 
informed consent and respect for potential and enrolled 
subjects (Emanuel et al., 2000). They describe the ethical 
principles for these responsible actions thusly, “Respect 
for potential and enrolled subjects is justified by multiple 
principles including beneficence, nonmaleficence, and 
respect for persons. Permitting subjects to withdraw and 
providing them additional information learned from the 
research are key aspects of respecting subject autonomy. 
Protecting confidentiality and monitoring well-being are 
motivated by respect for persons, beneficence, and 
nonmaleficence.” Section 4 already has described some 
of the particular concerns regarding privacy, 
confidentiality, and other issues related to observational 
human exposure studies. This section further describes 
elements of the relationship between researchers and 
participants that are important to consider and address 
during design and implementation of a study. 


and Researcher 


Of course, the relationship between the researchers 
and the individual participants does not exist in isolation. 
The researcher-participant relationship may influence 
and be influenced by the relationship with the 
community in which the participant lives. Good, two- 
way communications are critical for the development 
and nourishment of an appropriate researcher-participant 
relationship. Although those two topics are the subject of 
the next sections of this document, elements from those 
topics unavoidably will color the discussions in this 
section as well. 

Researcher training is a key component for 
conducting research that incorporates human subject 
protections and fosters appropriate researcher-participant 
relationships. Most organizations require basic human 
subjects training on the essential elements for processes 
and procedures for research with human subjects. More 
in-depth training will improve researcher understanding 
in areas of the informed consent process, observational 
techniques, community-based research, and other topic 
areas. Such training will benefit principal investigators 
throughout the research study from the design stage 
through communication of research results. Training is 
also important for staff that will work directly or 
indirectly with research participants or their samples and 
data. This document can be used as both a training tool 
for researchers as well as a resource for designing 
training courses. There are a number of sources of 
training on human subjects protection. The 
Collaborative Institutional Training Initiative (CITI, 
http://www.citiprogram.org/ ) is a subscription service 
providing research ethics education to many institutions. 
Other training, such as that provided by the National 
Cancer Institute ( http://cme.cancer.gov/clinicaltrials/lear 
ning/humanparticipant-protections.asp ) and the U.S. 
Department of Health and Human Services 


51 







( http://www.hrsa.gov/humansubiccts/dcfault.htm ), are 
available on-line. 

5.1 Informed Consent 

In observational human exposure studies, informed 
consent ensures that the participant accurately 
understands the range of risks and benefits (if any) 
associated with participation; emphasizes the voluntary 
nature of their participation; and provides essential 
protections to the participant. The three “pillars” of the 
informed consent process are (1) information; 
(2) comprehension; and (3) voluntary participation, or 
“voluntariness” (U.S. DHEW, 1979). Informed consent 
requires “provision of information to subjects about the 
purpose of the research, its procedures, potential risks, 
benefits, and alternatives, so that the individual 
understands this information and can make a voluntary 
decision whether to enroll and continue to participate” 
(Emanuel et al., 2000). 

The NRC & IOM document Ethical Considerations 
for Research on Housing-Related Health Hazards 
Involving Children (NRC & IOM, 2005) contains a 
comprehensive and very useful discussion of informed 
consent procedures and requirements in Chapter 6. The 
IOM report. Responsible Research: A Systems Approach 
to Protecting Research Participants , also includes a 
thoughtful discussion of participant-investigator 
interactions and the informed consent process (IOM, 
2002). CIOMS also includes recommendations for both 
the process and content of informed consent (CIOMS, 
2002). Some of the important points from those 
documents are summarized in Text Box 5-1, but the 
reader should refer to those documents for additional 
information about this topic. 

Federal regulations governing research that is either 
Federally conducted or Federally funded (i.e., all human 
subjects research at NERF) are codified in the Common 
Rule. The regulations set forth requirements for both the 
content of an informed consent and the process for 
obtaining and documenting an individual’s informed 
consent (see Text Box 5-2). 1 General regulatory 
requirements for the elements of informed consent are 
codified in the Common Rule at 40 CFR 26.116(a)(1)- 
(8) (CFR, 2006). The regulations also prescribe the use 
of a written consent form and describe how informed 
consent is to be documented (at 40 CFR 26.117). The 
regulatory requirements for informed consent highlight a 
number of issues that a NERF researcher needs to 


16 An IRB may waive informed consent under some very limited conditions. 
See 40 CFR 26.116(c) and (d). 


consider in developing and administering the informed 
consent process and the consent form document. The 
discussion of these issues, arising from regulatory 
requirements or identified in recent writings on ethical 
considerations in human subjects research, is grouped 
below, under the three pillars of informed consent: 
(1) information, (2) comprehension, and (3) voluntary 
participation. 

Text Box 5-1. Recommendations for Informed Consent j 
In the United States and Internationally 

(1) Revitalize Informed Consent (IOM, 2002) 

Informed consent is a process, not a form. It is an on-going, 
interactive dialogue between research staff and research 
participants with disclosure and exchange of relevant 
information, including assessment of understanding. 

Ethics Review Boards should ensure that the focus of both the 
informed consent process and the consent forms is on 
informing and protecting participants, not the research 
institution. 

(2) Strengthen Process of Parental Permission and 
Children’s Assent if Children Are Involved in Research 

(NRC & IOM, 2005) 

The process begins with a community-based discussion and 
concludes with an assurance that individual parents 
understand the essential elements of the research. 

Educate parents on issues critical to informed decision making 
and assess their degree of understanding. 

Use informational materials in the form that is most 
appropriate to convey information to potential participants. 
Consult with community representatives to ensure that 
information is complete, clear, and understandable, and that 
any payment will not be exploitive. 

Expand the perspective about what information about risks 
and benefits is needed to make an informed choice. 

Ethically, it is critical to assure that participants and parents 
understand the crucial features of the research effort. 

(3) Informed Consent Is a Decision To Participate by an 
Informed, Competent Individual Without Undue Coercion, 
Influence, or Intimidation (CIOMS, 2002) 

Informed consent is a process that takes time and resources. 

It is not a ritual recitation of text from a form but informative 
communication in language that suits the individual's level of 
understanding. 

Consent is ethically obtained, considering language and 
cultural issues, and is documented. 

Material changes in conditions or procedures require that 
informed consent be renewed. 

Consent should explain how samples will be used in current 
research, and, if applicable, how samples may be used in 
future research. 


5. 1.11nformation 

Some items that researchers should keep in mind as 
they provide information to the study participants are 
summarized below. These items may be based on 
regulatory requirements or currently may be 
recommendations as ethical “best practices.” 


52 










Text Box 5-2. Common Rule Requirements: 
Elements of Informed Consent 

(1) An explanation of the purposes of the research 

(2) The expected duration of the subject's participation 

(3) A description of the procedures to be followed and 
identification of any experimental procedures 

(4) A description of any reasonably foreseeable risks or 
discomforts to the subject 

(5) A description of any reasonably expected benefits to the 
subject or others 

(6) A disclosure of appropriate alternative procedures that might 
be advantageous to the subject 

(7) A description of the extent that confidentiality will be 
maintained 

(8) For research involving more than minimal risk, an 
explanation about whether compensation or medical 
treatments are available if injury occurs 

(9) An explanation of whom to contact with questions about the 
research or to report a research-related injury 

(10) A statement that participation is voluntary, refusal to 
participate will involve no penalty, and the subject may 
discontinue participation at any time without penalty or loss 
of benefits to which the subject is otherwise entitled 

(11*) A statement that the particular treatment or procedure may 
involve risks to the subject (or to the embryo or fetus, if the 
subject is or may become pregnant) that are currently 
unforeseeable 

(12*) Anticipated circumstances under which the subject's 

participation may be terminated by the investigator without 
regard to the subject's consent 

(13*) Any additional costs to the subject that may result from 
participation in the research 

(14*) The consequences of a subject's decision to withdraw from 
the research and procedures for orderly termination of 
participation by the subject 

(15*) A statement that significant new findings developed during 
the course of the research that may relate to the subject's 
willingness to continue participation will be provided to the 
subject. 

(16*) The approximate number of subjects in the study 

* Included if appropriate [40 CFR 26.116(b)] 


• The information “shall be in language understandable 
to the subject” (40 CFR 26.116). This may require 
forms to be written and administered in different 
languages during a study. For example, the National 
Children’s Study (NCS) plans to produce all consent 
materials in English and Spanish, with other 
translations made available as needed (NCS, 2007). 
Ethically, “language understandable to the subject” 
goes beyond simply using the appropriate language; 
the researcher is compelled also to consider 
readability and vocabulary (e.g., avoiding jargon or 
terminology that may be clear to the researcher but 
which may confuse or intimidate the potential subject) 
if the information is to be understandable. 

• Information may be presented orally in addition to an 
appropriately written document (40 CFR 26.117). 


Participants often find discussions with research staff 
more useful than written consent forms (p. 103, NRC 
& IOM, 2005). NCS plans to pilot test an interactive, 
computer-based audio/video consent tool and to 
compare it with traditional written informed consent 
approaches (NCS, 2007). 

• The information being discussed, including the 
explanation of the purpose of the research and the 
description of the study procedures, should be written 
or discussed at a level that the participant can 
understand. The National Institutes of Health 
recommends writing consent forms as “plain language 
documents that explain the research in an honest, 
straightforward way” and suggest that doing so will 
help enhance public trust (Recommendation 11, NIH, 
2005). 

• The consent form should contain sufficient 
information to describe the study procedures, but not 
so much information that it causes confusion and 
results in the participant not understanding the study. 
There is not agreement on what the appropriate level 
of information is. IRBs do not agree on the level of 
information; some require lengthy descriptions of the 
study, whereas others prefer concise information. 
Ultimately, the IRB dictates the language of the 
informed consent document, and the researcher will 
need to comply. It will benefit the researcher to 
discuss the consent process with their IRB when they 
develop the consent form document and process (p. 
108, NRC & IOM, 2005). 

• In observational human exposure studies, information 
about the risks of the hazards being studied needs to 
be conveyed to the participants during the consent 
process. Information should be provided to the study 
participant on what hazards pertinent to the topic of 
the study may be present in the participant’s 
environment, particularly those microenvironments 
being studied, what hazards will continue to exist in 
those microenvironments after the research is 
completed, and how those hazards may adversely 
affect the participant’s health (NRC & IOM, 2005). 

• The informed consent process should describe 
whether any study results will be provided to 


17 A survey of IRBs found that their readability standards ranged from 5th- to 
lOth-grade level (Paasche-Orlow et al., 2003). Interestingly, the same report 
found that, 92% of the time, the sample consent forms provided by the IRBs 
did not meet their own readability standards. The NRC & IOM report (p. 107, 
NRC & IOM, 2005) discusses an NCI effort to simplify informed consent 
forms by using text targeted at 8th-grade reading level. More information 
about the NCI template may be found at 

www.nci.nih.gov/clinicaltrials/understanding/simplification-of-informed- 

consent-docs/page2 (accessed September 12, 2007). 


53 










participants and, if so, how and when (p. 101, NRC & 
IOM, 2005). 

• For studies involving children as participants, it 
generally is regarded as desirable that the informed 
consent process should involve both parents 
(assuming that there are two competent parents 
available), and that the consent of both parents be 
obtained, if possible. The IRB may decide that the 
permission of one parent is sufficient, but only when 
certain risk-benefit conditions are met. iN 

• For studies involving children as participants, it is 
desirable for those children with sufficient capacity to 
be involved in the consent process. Moreover, it is 
generally accepted that the child’s assent be obtained 
whenever this is developmentally possible and 
otherwise appropriate. Under both the EPA Rule and 
the HHS Rule, the IRB is responsible for determining 
that adequate provisions have been made for soliciting 
the assent of the children when, in the judgment of the 
IRB, the children are capable of providing assent. 
Assent, however, may be waived in those restricted 
circumstances in which consent may be waived under 
the Common Rule. Those circumstances and the 
required IRB documentation are described in the 
Common Rule at 40 CFR 26.116(d). 

• The consent form should clearly state that 
participation is voluntary and that study participants 
may “discontinue participation at any time without 
any penalty or loss of benefits to which the subject is 
otherwise entitled” [40 CFR 26.116(a)(8)]. If a subject 
chooses to withdraw from a study, the consequences 
of their decision and the process for orderly 
withdrawal should be clearly explained [40 CFR 
26.116(b)(4)]. 

• The consent form should address any foreseeable 
potential future use of samples and data (CIOMS, 
2002). For example, effects of environmental 
exposures on gene expression are potentially very 
important. Therefore, biologic specimens for DNA 
analysis may be obtained from participants in future 
studies. But, it is recognized that human genomic data 
are private, intimate, and sensitive, and they create 


18 See the EPA Rule at 40 CFR 26.406(b) for observational research with 
children and the HHS Rule at 45 CFR 46.408(b) for all research with children. 
Under the EPA Rule, greater than minimal risk observational research with 
children that does not hold out the prospect of direct benefit to the child is not 
permitted under any circumstances. Under the HHS Rule, greater than 
minimal risk research involving children without the prospect of direct benefit 
is permitted in very limited circumstances, but the consent of both parents is 
required in those cases (unless one parent is deceased, unknown, incompetent, 
or not reasonably available, or when only one parent has legal responsibility 
for the care and custody of the child). 


special concerns about the potential for 
discrimination, stigmatization, and impact on future 
employment or insurance. The informed consent 
process needs to explain what the plans may be for 
such specimens and recognize the rights of the 
subjects to decide about any such future use, including 
having the material destroyed. The informed consent 
process needs to explicitly discuss obtaining 
permission from participants on behalf of themselves 
and their child to obtain specimens for genetic 
analysis. 

5.1.2 Comprehension 

Research participants frequently fail to understand 
the research protocols in which they agree to participate 
(NRC & IOM, 2005). In considering the ethical issues 
raised by the Grimes v. Kennedy Krieger case, the NRC 
& IOM committee “realized that the crucial issue 
regarding consent was not what information wa c 
contained in the consent forms, but rather what f 
parents understood about the study and the haza 
present in the home before and after the study” (p. h 
NRC & IOM, 2005). The committee laments that “IRBl 
place their attention on consent forms rather than on the 
process of providing and discussing information” (p. 
103, NRC & IOM, 2005). The IOM recommends that 
“the informed consent process should be an on-going, 
interactive dialogue between research staff and research 
participants involving the disclosure and exchange of 
relevant information, discussion of that information, and 
assessment of the individual’s understanding of the 
discussion” (Recommendation 4.1, IOM, 2002). These 
comments emphasize how important true two-way 
communication is to comprehension, the second pillar in 
the informed consent process. 

The following items are a variety of issues 
concerning comprehension that NERL scientists should 
keep in mind as they develop an informed consent 
process in collaboration with the research team, the IRB 
and other peer reviewers, and EPA’s HSRRO. These 
items may be based on regulatory requirements or may 
simply be recommendations as ethical “best practices.” 

• Researchers need to assume responsibility for 
developing an interactive dialogue with participants 
for the exchange and discussion of relevant 
information as a part of the informed consent process, 
not just for conveying information. The dialogue 
should be ongoing, continuing throughout the research 
project (IOM, 2002). 

• The consent form and its content are only one part of 
the overall consent process. An equally important part 


54 



is how information is conveyed to the participant 
outside of the written form itself. Participant 
comprehension is contingent on all elements of a 
comprehensive consent process that involves ongoing 
information exchange between researchers and 
participants, as well as a written informed consent 
document (NRC & IOM, 2005). 

• The most effective way to improve comprehension is 
by talking one-on-one with study participants. 
“Having a study team member or a neutral educator 
spend more time talking one-on-one to study 
participants appears to be the most effective way of 
improving research participants’ understanding” 
(Flory and Emanuel, 2004). 

• The information being exchanged (e.g., explanation of 
the purpose of the research, description of the study 
procedures) should be written at a level that the 
participant can understand (NRC & IOM, 2005). 

The researcher should describe the benefits of 
irticipation in the study [40 CFR 26.116(a)(3)], but 
tould not promise any outputs or outcomes that he or 
she cannot deliver. Participants often misunderstand 
-'the purpose of the research. The researchers also 
should attempt to reduce the likelihood of “therapeutic 
misconception” 19 or related misunderstandings in 
which the participant anticipates a benefit that does 
not really exist, such as reduction of the hazard in an 
observational study (NRC & IOM, 2005). 

• The consent procedure should include some test of the 
participants to demonstrate that they truly understand 
the information that is being conveyed (IOM, 2002). 

• Tools to assess comprehension have been developed, 
but, as described in NRC & IOM (2005), there are no 
standard mechanisms for assessing comprehension. 
Tests for appropriate grade-level language can be 
performed, but additional comprehension testing 
should be considered as well (Flory and Emanuel, 
2004). 

• Researchers need to develop innovative approaches to 
improve comprehension. Multimedia, such as video or 
graphics, may be used but have had limited success in 
the past (NRC & IOM, 2005; Flory and Emanuel, 
2004). NCS currently is developing a highly 
sophisticated video consent tool that may be able to 


19 Therapeutic misconception is a term that refers to an inaccurate 
understanding on the part of a research participant that a direct therapeutic 
benefit will be provided by virtue of participation in a clinical trial. 
Researchers performing observational human exposure studies should be 
aware of the potential for misunderstandings to arise that are analogous to the 
misunderstanding represented by the therapeutic misconception. Ensuring 
comprehension of the study and its expected results is important to this issue. 


serve as a model going forward. The video 
presentation will include embedded questions to 
assess the participant’s understanding of the key 
elements of NCS and what their participation will 
involve (NCS, 2007). 

• Development of written materials with appropriate 
languages and comprehension levels is only part of 
the communication challenge. In communities where 
languages other than English are spoken, it will be 
important that the research team be able to 
communicate orally with participants, often in ad hoc 
situations. Research protocols should address how 
translations will be accomplished. The use of 
untrained persons such as co-workers usually will not 
meet requirements for full understanding of human 
subject protections. Researchers should make plans 
for trained staff or trained community members, 
associated or affiliated with the research study, to be 
available for translations. 

5.1.3 Voluntary Participation 

The third pillar of informed consent is voluntary 
participation. The Belmont Report emphasizes that 
participants “should understand clearly the range of risk 
and the voluntary nature of participation” [emphasis 
added]. The ethical principles of respect for persons and 
their autonomous decisions morally obligate the 
researcher to ensure that an individual’s decision to 
participate in a human research study is truly voluntary 
and uncoerced (Emanuel et al., 2000). A number of 
study characteristics may affect whether the participant’s 
actions are truly voluntary. 

• Access to study-dependent benefits or care that would 
otherwise not normally be received may impair 
voluntariness. 

• Voluntary participation also may be compromised 
when there is an existing relationship between the 
researcher and participants, such as employer and 
employee or teacher and student. 

• Restricted voluntariness may be an intrinsic part of 
belonging to certain vulnerable groups, including 
children, prisoners, handicapped persons, mentally 
disabled persons, and economically or educationally 
disadvantaged persons, or members of the military, for 
example. When research participants come from such 
groups, additional protections to insure voluntariness 
in the context of the research may be required (see 
also 40 CFR 26, Subparts B, C, and D). 

• Payments as incentives may have undue influence and 
are discussed below. 


55 



• Whether payments will lead to a coerced decision to 
participate often is difficult to determine without input 
from people from similar socioeconomic backgrounds 
as the participants (p. Ill, NRC & IOM, 2005). 
Researchers should work with community 
representatives to develop a consent process that will 
be maximally effective in providing information, 
ensuring and documenting comprehension, and 
ensuring that participation is voluntary (also see 
Section 6). 

Researchers should remember that obtaining 
informed consent should be “an on-going, interactive 
dialogue . . . involving the disclosure and exchange of 
relevant information” (IOM, 2002): it is not simply 
having a consent form signed. The process is most 
effective when the researcher spends time with potential 
participants to discuss the study and to answer questions. 

5.2 Payments to Research Participants 

The decision whether to pay research participants, 
including the appropriate level of payment, 211 is a 
complex ethical issue. Monetary or nonmonetary 
payments are not ethical if they constitute an undue 
inducement for participants to assume research risks that 
they would not otherwise accept. On the other hand, it 
may be ethically appropriate to offer reasonable 
payments in some research studies. Indeed, payment of 
human subjects for their participation in scientific 
research is a common practice in the United States, with 
a history of well over 100 years (Grady, 2005). The 
difficulty for researchers and IRBs is that there is often 
little clear and uniform guidance for determining what 
constitutes “undue inducement” or “reasonable” 
payment for any particular research study, population, 
and level of risk. Additional considerations regarding 
payment to participants arise when working with 
vulnerable populations, including children. 


There are many terms that may be found in the literature to describe both 
monetary and nonmonetary payments, like payment, remuneration, 
compensation, recompense, incentive, inducement, reimbursement, and 
reward. Each of these words has its own definition, and each word also may 
carry specific connotations. In general, these terms refer to money or other 
items that “are often given to acknowledge the time and inconvenience of 
participating in research or to reimburse participants for any costs they incur. 
The term compensation is often used in the context of compensation for 
research-related injuries” (p. 112, NRC & IOM, 2005). The authors have 
chosen to use “payment” as the general term for monetary and nonmonetary 
items provided to research subjects for their participation in the research. They 
may occasionally refer to compensation for research-related injuries, but the 
text should make it clear when they do. 


5.2.1 Types and Amounts of Payments Offered 
in Research Studies 

Payments have been offered in a wide variety of 
research studies, ranging from clinical trials to 
behavioral and social research to observational human 
exposure studies. Payments can take various forms, 
including monetary payments (e.g., cash, gift 
certificates, reimbursement for expenses), nonmonetary 
payments (e.g., gifts, valuable information), or nothing 
at all (e.g., for a sense of altruism). Grady (2005) has 
described payment for the participation of research 
subjects as serving from one to four purposes: (1) an 
incentive, (2) compensation, (3) reimbursement, or 
(4) reward. Text Box 5-3 describes the roles that 
payments may serve, together with potential advantages 
and disadvantages or ethical concerns. The text comes 
mostly from Grady (2005) but builds also on the NRC & 
IOM document and other writings. (A number of authors 
have addressed issues associated with payments, 
including Ackerman, 1989; Dickert et al., 2002; 
Emanuel 2004; Erlen et al., 1999; Fry et al., 2005; 
Grady, 2005; Grady et al., 2005; litis et al., 2006; IOM, 
2004; NRC & IOM, 2005; Russell et al., 2000; 
VanderWalde, 2005; Weise et al., 2002; Wendler et al., 
2002). A number of specific issues or concerns 
regarding participant payments have been identified. 
Many researchers and ethicists argue that it is often 
appropriate to provide reasonable payment and have 
done so for many years. In the view of an NRC expert 
panel, the principles of “justice, fairness, and gratitude 
support payment to those who bear the burdens of 
research on behalf of society” (NRC, 2004). 

Direct reimbursement may be made to participants 
for out-of-pocket expenses for costs directly associated 
with participation in a study. These might include 
transportation costs, parking fees, or child care costs. 
When payment for time and burden is provided, it is 
often in the form of monetary payments. Different 
approaches may be considered for determining 
reasonable amounts for payment, including a set 
payment for each visit, a small daily payment, payment 
at the prevailing minimum hourly wage, or payment at 
some other hourly rate appropriate for the 
community—perhaps a prevailing rate for unskilled 
labor (Emanuel, 2004). Incentives to encourage 
enrollment are sometimes used when participants will 
receive little or no direct benefit from the research and 
can take the form of monetary or non-monetary 
payments. Incentives are kept modest so as not to impart 
undue influence. Researchers need to consider the 
possible effects of incentive payments on the potential 


56 




Text Box 5-3. Payments for Participation of Research Subjects 

(based on Grady, 2005) 

Payment Serves As 

Amount Determined By 

Potential Advantages 

Potential Disadvantages 

Incentive 

Supply and demand; market 

(a) More rapid recruitment 

(a) Undue inducement possibly resulting 


rates 

(b) Completion bonuses encourage 
subject retention and high 
completion rate 

(c) Possibility of profit for participants 

(d) Little or no financial sacrifice by 
subject 

in incomplete assessment of risks 
and benefits by subject; subject 
concealing information to ensure 
enrollment and retention 

(b) Competition between studies; better 
funded studies more likely to meet 
recruitment goals 

(c) Different levels of payment at 
different locations for multicenter 
research because of supply and 
demand 

Compensation 

Standardized “wage” for time 

(a) Recognizes contributions of 

(a) May have little impact on recruitment 


and effort, suggested to be 

participants 

(b) Might undercompensate some 


commensurate with wages for 

(b) Uniform payment across studies 

subjects in relation to regular wage 


unskilled, but essential jobs; 
additional payment for extra 
burdens such as endurance of 
uncomfortable procedures 

(c) Equal pay for equal work 

(d) Less risk of undue inducement 

and preferentially attract others 


Provide "wage” for time and 

(a) Recognizes contributions of 

(a) Different levels of payment at 


effort; base level of payment 

participants 

different locations in multicenter 


on some small fraction of 

(b) Decreases potential that payment 

research or in different communities 


participant’s or the 

would be undue inducement in 

(b) Unequal pay for equal work may 


community’s income, or on an 
appropriate hourly rate for the 
location, or on community-input 
about the appropriate level of 
payment 

some communities or locations 
and insufficient in others 

(c) Provides equivalent payment for 
participation across communities 
and locations (markets) 

(d) Less risk of undue inducement 
across study 

violate one’s sense of justice 

Reimbursement 

Actual out-of-pocket cost to 

(a) Lowers barriers to participation 

(a) Few disadvantages 


participant related to 

(b) Reduces burden and impact of 

(b) Possible differences in costs 


participation, such as parking, 
transportation, child care, cost 
of food samples, etc. 

research on participants 

experienced by different participants 

Reward 

Token of appreciation at end of 

(a) Expresses gratitude for 

(a) Probably no impact on recruitment 


study 

contribution made 

(b) Not market dependent 

(c) Avoids undue inducement 

(b) No basis for consistency 


for differential recruitment that could result in bias in the 
study sample. 

Determining appropriate level of payments or 
incentives for participants in a research study is 
complex. “No bright line distinguishes proper and 
reasonable payments to parents and children from 
payments that are inappropriate” (p. 214, IOM, 2004). 
The ethical issue is at what level might a payment 
change from being an incentive (an encouragement) to 
participate and become an inducement (the cause or 
reason) for participation. Many research organizations 
and IRBs do not have written policies or guidelines 


regarding the determination of reasonable payment. 
Decisions often are made based on the level of 
discomfort and burden, costs to participants, and 
population characteristics. However, large differences in 
payment levels have been found even in multisite studies 
in which the same protocol is administered across all 
sites. 

Grady et al. (2005) performed a survey of practices 
for paying research participants in the United States in 
Phase 1 to 4 clinical trials and physiologic, behavioral, 
and other types of research. Across 467 studies of 
varying complexity that included payments, the median 


57 












payment was SI55 (mean S266, range $5 to $2,000). The 
basis for dollar amounts was infrequently described, 
with 19% of the payments based on time, and 12% based 
on the procedures. In a model of payment factors, 
studies with some prospect of therapeutic benefit, studies 
having at least one invasive procedure, and studies with 
greater numbers of clinic visits were significantly 
associated with higher dollar amounts. About 9.5% of 
the studies offered completion bonuses, and a similar 
percentage offered escalating payments for followup 
study visits. 

5.2.2 Regulations and Guidance Regarding 
Payment to Research Participants 

There is little specific guidance regarding payments 
in Federal human research regulations. The Common 
Rule and additional human subjects protections do not 
directly address payments to research participants, but 
the regulations do discuss providing additional 
safeguards for subjects vulnerable to coercion or undue 
influence [40 CFR 26.111(b)]. The NIH IRB guidebook 
advises IRBs to determine whether the rewards offered 
for participation in research constitute undue influence 
(U.S. HHS, 1993). According to the IRB guidebook 
undue inducement might blind prospective subjects to 
risks, impair their ability to exercise proper judgment, or 
may cause people to lie or to withhold information that 
would make them ineligible to enroll or continue 
participation. 

The U.S. Food and Drug Administration (FDA) has 
provided guidance for investigators and IRBs for clinical 
research studies (FDA, 1998). The guidance states that 
“payment to research subjects for participation in studies 
is not considered a benefit, it is a recruitment incentive.” 
FDA expects payments to accrue as the study progresses 
and not to be contingent on completing the study, 
although a “small proportion as an incentive for 
completion of the study is acceptable.” The guidance is 
concerned with the issue of coercion or undue influence, 
and it recognizes the IRB as the responsible party for 
deciding what is or is not acceptable. 

The U.S. Office of Management and Budget (OMB) 
develops standards and guidelines for statistical surveys 
performed by the Federal government. Under Guideline 
2.3.2, OMB states that, while incentives are not typically 
used in Federal surveys, agencies may consider use of 
respondent incentives if they believe incentives would 
be necessary to use for a particular survey to achieve 
data of sufficient quality for their intended use (OMB, 
2006a). OMB requires that agencies provide a 
justification for giving incentives to respondents. Some 


of the factors cited by OMB to be addressed include 
those particularly relevant to observational human 
exposure studies, including unusual reporting burdens 
(keeping data logs for extended periods, coordinating 
study team visits, participating in a medical examination, 
etc.), complex study designs (such as studies requiring 
ongoing participation of respondents), and past 
experience, especially when there is evidence of attrition 
or poor response rates (OMB, 2006b). Although OMB 
primarily considers incentives with regard to survey 
response rates and data quality, researchers need to 
consider payments to participants, including 
participation incentives, in the broader context discussed 
in this section. 

CIOMS also provides guidance and commentary on 
this issue in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (2002). 
Guideline 7 and the associated commentary emphasize 
that payments to subjects for expenses incurred because 
of their participating in a research study are legitimate. 
The guideline also allows payment for inconvenience 
and time spent, so long as the payments or other direct 
benefits are not “so extensive as to induce prospective 
subjects to consent to participate in research against their 
better judgment.” 

The approaches of HHS, FDA, and CIOMS above 
are consistent in not considering payments to be a 
benefit to research participants when considering risks 
versus benefits. All of the guidelines recognize the 
legitimacy of some recompense, but they all are 
concerned with the issue of undue influence. “Payments 
or rewards that undermine a person’s capacity to 
exercise free choice invalidate consent” (CIOMS, 2002), 
and voluntariness is a pillar of legitimate informed 
consent. 

Text Box 5-4 lists some of the concerns about, and 
the reasons for, payment of participants. 

IRBs have considerable discretion with regard to 
payments and consider payments with regard to the 
specific circumstances of the research and of the 
population being studied. The issue of recompense can 
be a difficult but legitimate ethical issue involving 
weighing the different ethical principles of justice and 
fairness against the concerns about undue influence and 
the invalidation of consent. Ethical review committees, 
including IRBs, need to consider many factors when 
determining when it is appropriate to offer payments to 
research participants and the level and form of payments 
when they are appropriate. Review committees also 
should consider how and when information on payments 
is communicated to prospective study participants. 


58 


Text Box 5-4. Weighing the Ethical Issues 
About Payments 


Concerns about Payments 

• Payments may compromise 
voluntary participation. 

• Participants may accept risks 
they would not otherwise 
accept. 

• Participants may continue in a 
research study beyond a point 
they might ordinarily have 
withdrawn. 

• Payments may differentially 
encourage research 
participation by economically 
disadvantaged people. 

• The offer of payments may 
cause guardians or parents to 
not act in the best interests of 
incompetent persons or children 
in their care. 

• Persons in different 
circumstances may view the 
same amount of payment quite 
differently. 

• Payments may alter the 
composition of the study sample 
and potentially could 
compromise study integrity. 


Reasons for Payments 

• Recognizing participant 
contributions to the 
research and knowledge 
gained 

• Providing reimbursement 
for direct and indirect 
participant costs 

• Providing reasonable 
payment for the time and 
effort associated with 
participation in research 

• Providing incentives for 
participation in studies 
with low risk but no or few 
direct benefits 

• It is the just and fair thing 
to do for those who bear 
burdens of research on 
behalf of society. 


5.2.3 Payments When Children or Other 
Vulnerable Populations Are Involved 

It is essential that special care be taken with regard 
to payments when members of vulnerable populations 
are included in research studies. Vulnerable populations 
may include children and adolescents, those with 
cognitive impairments because of medical conditions or 
age, economically disadvantaged persons, and prisoners. 
These populations often are not capable of making 
autonomous, fully informed decisions regarding risks 
and benefits, or they may be particularly vulnerable to 
undue influence resulting from the offer of a payment for 
research participation. In addition, payments made 
directly to parents or guardians could alter judgment 
regarding the best interests of minor or incompetent 
persons in their care. 

The ethical concern is that too high a payment may 
“undermine free and informed consent by leading 
parents to expose their children to unacceptable risks” 
(NRC & IOM, 2005). The NRC & IOM committee 
recognized that some commentators argued that children 
should never be paid, and that parents ought not to be 
paid to enroll their children in research. Yet, on balance, 
the committee felt that “reimbursement for expenses and 
some modest payment for time spent in research 


activities is thus justified on the grounds of fairness” (p. 
112, NRC & IOM, 2005). 

Similarly, the IOM Committee on Clinical Research 
Involving Children found that “certain types of 
payments to parents or adolescents are usually if not 
always acceptable, for example, reimbursement for 
reasonable expenses that are necessary for research 
participation. The specifics may vary, but examples of 
reasonable expenses are costs of transportation to the 
research site, parking, lodging, meals, and babysitting. 
Other payments are never appropriate in pediatric 
research, for example, paying parents for the use of their 
child in research” (pp. 225-6, IOM, 2004). 21 

The IOM committee recommends establishing 
policies on acceptable and unacceptable types of 
payments. They also recommend that the policies 
disclose any recompense in a full and open process, 22 
while not overemphasizing any recompense. 

Although the NRC & IOM Committee on Ethical 
Issues in Housing-Related Health Hazard Research 
Involving Children and the IOM Committee on Clinical 
Research Involving Children both concluded that it is 
appropriate to reimburse expenses or compensate for 
time or inconvenience, neither committee endorsed 
incentive payments to parents. In Europe, too, incentive 
payments to induce parents to allow their children to 


21 

The IOM Recommendation 6.2 states, “In addition to offering small gifts or 
payments to parents and children as gestures of appreciation, investigators 
may also—if they minimize the potential for undue influence—act ethically to 
reduce certain barriers to research participation when they 

• reimburse reasonable expenses directly related to a child’s participation in 
research 

• provide reasonable, age-appropriate compensation for children based on 
the time involved in research that does not offer the prospect of direct 
benefit, and 

• offer evening or weekend hours, on-site child care, and other reasonable 
accommodations for parental work and family commitments.” 

~>2 

" In recommending an open process, the IOM committee chose to reject the 
arguments from the American Academy of Pediatrics that “any token payment 
to children for participating in research should not be discussed with them 
until after research is completed for fear of unduly influencing their decisions 
(AAP, 2003).... On balance, the committee agrees that it is best to mention 
token or other payments during the permission and assent processes” (p. 215, 
IOM, 2004). 

Tire IOM Recommendation 6.1 states, “Institutional review boards, research 
institutions, and sponsors of research that includes children and 
adolescents should adopt explicit written policies on acceptable and 
unacceptable types and amounts of payments related to research 
participation. These policies should specify that investigators 

• Disclose the amount, the recipient, the timing, and the purpose (e.g., an 
expense reimbursement or a token of appreciation to a child) of any 
payments as part of the process of seeking parents’ permission, and, as 
appropriate, children’s assent to research participation; 

• Avoid emphasis on payments or descriptions of payments as benefits of 
participating in research during the permission or assent procedures; and 

• Obtain institutional review board approval for the disclosure of 
information about payments in advertisements and in permission and 
assent forms and procedures.” 


59 





participate in research are unacceptable. The European 
Union requires that clinical trials on minors be 
undertaken only if “no incentives or financial 
inducements are given except compensation” (European 
Parliament, 2001). 

Payment for participation of children in research 
also is discussed in the literature. Diekema (2005) 
emphasizes the need to ensure that payments do not 
distort parental decisionmaking and do not tempt parents 
to consider other issues than the welfare of their child. 
Similarly, Menikoff (2005) suggested that there need to 
be relatively robust protections in place to ensure that 
families do not change their behaviors to participate in a 
study. He suggested that these may include determining 
payment as a percentage of a family’s income and 
developing criteria for documenting that behaviors have 
not changed to be eligible for participation in a study. He 
suggested that, for a study of pesticides, potential study 
participants provide documentation (such as receipts) 
that they routinely have been using a commercial 
pesticide service. This may be difficult for potential 
participants to do if they do not save receipts, and it 
would exclude all potential participants who purchase 
products and apply pesticides themselves. This likely 
would affect the study objectives and generalizability of 
the data collected. A survey of investigators (litis et al., 
2006) found that payments were made in 52% of the 
pediatric research studies surveyed, and that payment 
practices varied, as did the reasons for decisions 
regarding payments. They found a range of payment 
values separated across cash, gifts, items, vouchers, and 
other categories. A survey of IRBs (Weise et ah, 2002) 
found that payment for participation in research was 
allowed by 66% of responding institutions, but that 
many IRBs did not have specific policies, and that there 
was considerable variability regarding the basis for 
decisions on payments in studies with children. The 
types of payments included money, certificates, and 
bonds with large ranges in the amounts of payments for 
approved pediatric research. This research shows a lack 
of consistency and the need for guidance and 
institutional policies that describe acceptable and 
unacceptable payments and the basis for the amount of 
any payments. 

The NRC & IOM Committee on Ethical Issues in 
Housing-Related Health Hazard Research Involving 
Children described many of the ethical considerations, 
practices, and policies regarding payments (NRC & 
IOM, 2005) for research conducted in the participants’ 
homes, rather than in a clinical facility. The research 
setting is similar to the setting of most observational 


human exposure studies, and the committee’s 
commentary and recommendations are also relevant. The 
committee notes that it would be unfair to expect 
families to make considerable sacrifices to participate in 
a time-consuming activity designed to advance 
generalizable scientific knowledge, rather than benefit 
themselves directly, and that payment for reimbursement 
of expenses and modest payment for time spent in 
research activities is justified on the grounds of fairness. 
But the committee then warns that if payments are too 
high, they may distort parents’ decisions about enrolling 
their children. The committee also found that '"how the 
payment is made may also result in undue influence. For 
example, if payment for a long-term follow-up study is 
made in a lump sum and only if the subjects complete 
the entire study, then it could constitute an undue 
influence to stay in the study. If, on the other hand, the 
money is paid weekly, the effect would not constitute an 
undue influence.” 

The NRC & IOM committee recognizes that the 
issue of payment for participation in research is 
controversial. They also discuss how “countervailing 
ethical guidelines” may complicate the issues even more. 
Citing Wendler et al. (2002), the NRC & IOM 
committee points out that payments that are trivial for 
some families may be substantial for low-income or 
disadvantaged families. “Yet to pay economically 
disadvantaged families less than more affluent families 
for participating in the research is unfair because it 
requires similar sacrifices of time and inconvenience 
from both” (p. 113, NRC & IOM, 2005). Similar ethical 
quandaries can arise in multisite studies with differing 
costs for living. If the same payment is used in high-cost 
cities as in low-cost areas, the payment may be 
inadequate to gain sufficient enrollment in the high-cost 
area, whereas the same dollar amount may be “coercive” 
in the low-cost area. The NRC & IOM committee notes 
that a similar situation can arise when a study enrolls 
participants from diverse socioeconomic backgrounds. 
There are social justice concerns that poorer people 
might incur a disproportionate share of research risk and 
burden if payments induce unequal participation rates in 
the population. Decisions regarding payment for 
research participation will require careful consideration 
by IRBs when economically disadvantaged people may 
be enrolled. Community advisory boards (CABs) can be 
very important in helping researchers and IRBs 
determine what is appropriate with regard to payments 
within their community. 


60 


5.2.4 Payments in Observational Human 
Exposure Studies 

Observational human exposure studies most often 
involve minimal risks to study participants and few 
direct benefits, but may require considerable time and 
burden for participation. Study requirements can include 
multiple in-home visits; the burden of wearing personal 
air monitors for one or more 24-hour period; preparing 
and providing duplicate diet samples; collection of 
environmental samples inside and outside the home; 
completing questionnaires, food diaries, and time- 
activity diaries; and providing urine, blood, saliva, or 
hair samples. Monetary payments often have been 
included in these studies, with the level of payment 
related to the number of study days or visits or the 
specific kinds of environmental and biological samples 
and information that are collected or provided. Payment 
for direct participant costs has been included in some 
studies, such as a reasonable payment for providing 
researchers with duplicate diet samples. 

NERL scientists should review the commentary and 
recommendations in the literature before devising a 
payment program as part of a research protocol, 
especially the two recent National Academies of Science 
documents, Ethical Issues in Housing-Related Health 
Hazard Research Involving Children (NRC and IOM, 
2005) and Ethical Conduct of Clinical Research 
Involving Children (IOM, 2004). They should seek 
guidance from EPA’s HSRRO to determine EPA’s latest 
policies and guidance in this regard. Input also should be 
sought from community representatives to ensure that 
any payment is adequate to compensate for expenses and 
reward participation, but that the payment is not so high 
as to constitute undue influence or coercion in the 
community. If the study includes several followup visits 
over a long term, NERL researchers should ensure that 
payment is made incrementally as the NRC & IOM 
committee suggested. NERL scientists also should adopt 
the IOM Recommendations 6.1 and 6.2, including 
ensuring that any payment should be for appropriate 
purposes and age-appropriate, and that the process 
should be open and fully disclosed, while not overly 
emphasizing payments during the recruiting or informed 
consent phases. The final decisions about the ethics of 
payments rest with the IRB, which will review, modify 
as needed, and approve the research protocol, and with 
the EPA HSRRO, who has final authority to approve, 
modify, or disapprove all of NERL’s human subjects 
research efforts. 


5.3 Research Rights and Grievance 
Procedures 

Protecting the research rights of participants and 
providing independent access to information regarding 
those rights and to grievance procedures is an important 
element in developing and maintaining appropriate 
participant-investigator relationships. As part of the 
informed consent process, the Common Rule requires 
“An explanation of whom to contact for answers to 
pertinent questions about the research and human 
subjects’ rights, and whom to contact in the event of a 
research-related injury to the subject” [40 CFR 
26.116(a)(7)], 

Information about the research often best can be 
answered by the researcher. However, it may benefit 
researchers and participants if information about the 
research can be obtained from or confirmed by a trusted 
independent person or organization. Participants also 
need to know how they can contact someone, 
independent from the researcher, who can answer 
questions concerning the rights of research participants 
and provide information on grievance procedures and 
research-related injuries. These questions could be 
addressed to the IRB, an ombudsman, an ethics 
committee, or other knowledgeable administrative body. 
Consent documents are expected to have at least two 
names with appropriate telephone contact 
information—one that can provide information 
regarding the research and another that can provide 
information regarding their rights as research 
participants. Grievance procedures should be structured 
so that grievances reach the approving IRBs and 
sponsoring organizations. 

5.3.1 Ombudsman 

An ombudsman is a neutral independent advocate 
for research participants (and their families or guardians, 
where applicable). Institutions and IRBs may 
recommend or require the use of an ombudsman in 
certain types of research studies, particularly those 
seeking to study vulnerable populations. Ombudsmen 
can fill several roles as participant advocates. They may 
be an independent source of information regarding the 
study. They may be present during the informed consent 
process to ensure that risks, benefits, and study 
requirements are communicated correctly and 
understood by potential participants or their guardians. 
An ombudsman may be used in studies involving 
prisoners or military personnel to ensure that there is no 
coercion to participate. And the ombudsman may 


61 



communicate problems or grievances raised by research 
participants to the IRB and sponsoring organization. 

5.3.2 Community Advisory Board 

CABs can help ensure that participant rights are 
considered and addressed during the study design and 
can play an important role in monitoring the research 
process. Community members may choose to seek 
information about the study from the advisory panel, as 
an independent entity, before deciding whether to enroll. 
Representatives from such advisory boards can be 
included in the research team that designs the study (see 
Section 2.3). The role of CABs is more fully discussed 
in Section 6. 

5.4 Creating a Supportive Environment for 
Research and Interaction 

It is recommended that researchers and institutions 
strive to create a supportive environment for research 
and interaction with research participants and 
communities. At the personal level, this means 
researchers building trust with individuals and treating 
them with respect. Following the IOM recommendations 
about the informed consent process—that it “should be 
an on-going, interactive dialogue between research staff 
and research participants involving the disclosure and 
exchange of relevant information, discussion of that 
information, and assessment of the individual’s 
understanding of the discussion” (Recommendation 4.1, 
IOM, 2002)—should go a long way in establishing a 
supportive environment with the individual participants. 
At the community level, engagement of the community 
throughout the design, conduct of the study, and follow¬ 
up will support trust-building and positive interactions. 
Developing and providing this kind of support can be 
challenging in large-scale studies, and particularly those 
that cross communities or are conducted across large 
geographic areas. Institutions need to recognize the need 
for, and value of creating supportive research 
environments by providing adequate funding because 
effective interaction takes considerable time and effort. 

Many of the factors that create a supportive 
environment for research participants are described in 
the Report and Recommendations on Public Trust in 
Clinical Research for the NIH Director from the 
Director’s Council of Public Representatives (COPR) 
(NIH, 2005). Although the advice from this workshop 
was developed in the context of NIH-supported clinical 
research, many of the recommendations are applicable to 
observational human exposure studies and human 
subject research in general. A summary of 


recommendations from the report for enhancing public 
trust is provided in Appendix D. The recommendations 
are focused on the following areas. 

• Building trust through community partnerships 

• Building relationships with patients (participants) 
(True partnerships with patients may not be possible, 
but bidirectional relationships must be enhanced.) 

• Building partnerships with community providers 

• Building trust in scientists 

• Building trust in the (EPA) and scientific research. 

5.5 Recruitment Strategies 

Many strategies are used to select and recruit people 
into research studies requiring human participation. The 
IRB is responsible for reviewing the selection process to 
ensure that it is, above all, equitable. The requirement 
for IRB review is stated in 40 CFR 26.11 l(a)3. 

Selection of subjects is equitable. In making this 
assessment, the IRB should take into account the 
purposes of the research and the setting in which the 
research will be conducted and should be particularly 
cognizant of the special problems of research 
involving vulnerable populations, such as children, 
prisoners, pregnant women, mentally disabled 
persons, or economically or educationally 
disadvantaged persons. 

The IRB guidebook is an excellent resource for 
consideration of concerns and elements for equitable 
participant selection (U.S. HHS, 1993). It states that 
“Defining the appropriate group of subjects for a 
research project involves a variety of factors— 
requirements of scientific design, susceptibility to risk, 
likelihood of benefit, practicability, and considerations 
of fairness.” The IRB guidebook raises a number of 
points to consider in the process for selection of human 
participants (see Text Box 5-5). 

Various participant recruitment strategies may be 
used depending on the type of research being performed 
and the population of interest. This section addresses the 
strategies and approaches for identifying and contacting 
people and subsequent recruitment into a research study. 
Sampling design approaches and issues, such as 
statistical issues regarding representative and nonrandom 
sampling designs, oversampling of subpopulations, and 
environmental justice considerations are part of the 
study design process described in Section 2 and are 
critical for deciding which recruitment approaches will 
be used. 


62 




Text Box 5-5. IRB Guidebook Issues on 
Identifying Subjects 

1. Who will bear the burden? Who will reap the benefits? 

2. Is there a disproportionate burden on any single group? 

3. Is the proposed subject population required or justified? 

4. Are there susceptible groups of people who should be excluded 
from the research? 

5. Are anticipated benefits distributed fairly? Do others have a 
greater need to receive any of the anticipated benefits? 

6. Are the research burdens distributed fairly? 

7. Will any special physiological, psychological, or social 
characteristics of the subject group pose special risks for them? 

8. Would it be possible to conduct the study with other, less 
vulnerable subjects? 

9. Has the selection process overprotected potential subjects who 
are considered vulnerable (e.g., children, cognitively impaired, 
economically or educationally disadvantaged persons, patients 
of researchers, seriously ill persons), so that they are denied 
opportunities to participate in research? 

10. If the subjects are susceptible to pressures, are there 
mechanisms to reduce the pressures or minimize their impact? 


Some of the common approaches for identifying and 
making initial contact with potential participants include, 
but are not limited to 

• direct telephone or in-person contact with a person 
selected through a statistical sampling process to 
obtain a representative sample of the population being 
studied; 

• use of print or other media advertisements, often used 
to recruit people in a community with specific 
characteristics; 

• advertisement or word-of-mouth contacts through 
community groups, civic organizations, or other types 
of organizations; and 

• recruitment at physicians’ offices, hospitals, and 
clinics or at churches, schools, or other social 
institutions, either in person or through the use of 
advertisements or study brochures. 

CABs can be consulted regarding proposed 
approaches for recruitment in community-based 
research. All procedures and materials for participant 
recruitment are reviewed and approved by the IRB prior 
to implementation. Some of the materials prepared for 
recruitment might include the following. 

• Recruitment scripts—prepared scripts used for in- 
person or telephone study information and recruitment 
contacts 

• Printed materials—brochures, flyers, newspaper 
advertisements, letters, and information articles 

• Audio/visual materials—radio and television scripts, 
video segments, public service announcements 

• Internet postings—study announcements and 

information, links to study materials, links to related 
information. 


The IRB reviews all recruitment material to ensure 
that it does not adversely affect the informed consent 
process, is consistent with the study protocol, and is 
likely to result in equitable participant selection. IRBs 
will carefully consider how information regarding 
payment for participation is presented to potential 
participants so as not to create undue influence. 

Participant recruitment may be performed directly 
by the researcher or staff members of the researcher’s 
organization, or other individuals or organizations may 
be asked to recruit or make initial informational contacts 
with potential participants. All persons involved in 
recruiting must adhere to the procedures and materials 
approved by the IRB. It is recommended that sponsoring 
organizations should not pay recruiters on a per- 
individual basis to minimize the likelihood that 
individual recruiters will put undue pressure on potential 
participants to enroll. 

5.6 Retention Strategies 

Some observational human exposure studies require 
only a single visit or a single set of visits with a 
participant over a relatively short time period (e.g., 24 
hours or 1 week). Other studies may involve repeated 
interaction with participants over longer periods of time. 
Longitudinal study designs require retention strategies 
that ensure that adequate sample sizes are maintained for 
meeting study objectives. It is recommended that 
researchers and IRBs evaluate the level of burden in 
longitudinal studies and ensure that retention strategies 
are not likely to create conditions of coercion or undue 
influence. 

Some of the common strategies for maintaining high 
retention rates in longitudinal studies are listed in Text 
Box 5-6. 


Text Box 5-6. Common Strategies for Maintaining High 
Retention Rates in Longitudinal Studies 

• Developing and maintaining a strong study identity 

• Building participant trust 

• Communicating regularly with participants 

• Providing feedback that is of use to participants 

• Maintaining confidentiality 

• Incorporating active participant tracking mechanisms 

• Maintaining reasonable levels of burden 

• Providing periodic tokens of appreciation 

• Providing reasonable levels of payment at each time point, 
sometimes including escalating payments or a higher final 
payment for completion of all study activities 


63 








It is important that strategies that use payments to 
encourage retention should be carefully scrutinized 
against the possibility that they will result in undue 
influence or diminish voluntary participation. Payments 
that cover expenses and for time and burden at each visit 
have to be reasonable, and researchers and IRBs should 
consider whether the cumulative level of payments over 
time or the use of escalating payments or final bonus 
payments might present undue influence on 
decisionmaking regarding participation. Participants 
have to feel capable of withdrawing from participation at 
any time, and escalating payments or completion 
bonuses can impact decisions to withdraw. Withholding 
all payment until all study visits are completed or 
making payment contingent on completing all activities 
is not an acceptable practice in most longitudinal studies 
because it can diminish the capacity for voluntary 
participation. (See the discussion about payment issues 
in long-term studies in Section 5.2.3.) 

People are more likely to continue active 
participation in longitudinal studies when they believe 
that the research is important, and that they are making a 
valuable contribution, are receiving regular feedback, 
and are treated with courtesy and respect by researchers. 
Observational human exposure studies sometimes 
involve substantial burdens of time and effort. Over long 
periods, this level of burden can reduce retention. It may 
be necessary to develop novel methods that reduce 
participant time and effort or to focus the study design so 
that fewer study procedures are implemented at any time 
point. Because the time needed to analyze samples, 
verify results, and perform data analyses can be long, it 
may be difficult to provide timely feedback to 
participants in observational human exposure studies. 
Researchers might consider including simple measures 
that can provide immediate and useful information of 
value to participants to encourage continued 
participation. Effective use of these strategies will 
reduce the need for higher payments to encourage 
retention. 

5.7 Ensuring Recruitment or Retention 
Methods Will Not Lead to Unacceptable 
Risk 

Researchers and IRBs need to ensure that the 
procedures and materials used to recruit and retain study 
participants in observational human exposure studies do 
not “undermine free and informed consent by leading 
parents to expose their children to unacceptable risks. 
(NRC and IOM, 2005)” Payments in these studies 
should not be so high that they would cause an undue 


inducement for a participant to use a product they would 
not normally use or to perform an activity that they 
would not normally perform. Not only would this bias 
the study results but may lead to higher than normal 
levels of exposure. Alternatively, the act of studying one 
set of conditions or activities in an observational human 
exposure study could lead participants to assume that 
those conditions or activities involve substantial risk. In 
response, they subsequently may change their activities 
in ways that could lead to possibly higher risks. The 
potential for such unintentional outcomes is difficult for 
researchers to gauge but requires researcher caution in 
how information and results are conveyed. However, if 
the informed consent process is truly “an on-going, 
interactive dialogue . . . involving the disclosure and 
exchange of relevant information,” then such 
misunderstandings should be minimized. 

References 

AAP (American Academy of Pediatrics Committee on 
Environmental Health) (2003). Pediatric and 
Environmental Health. (2nd Edition). Elk Grove Village, 

IL: American Academy of Pediatrics. 

Ackerman TF (1989). An ethical framework for the practice of 
paying research subjects. IRB 11(4): 1-4. 

CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I 
Environmental Protection Agency Part 26 Protection of 
Human Subjects. U.S. Code of Federal Regulations. 
Available: http://www.access.gpo.gov/nara/cfr/waisidx 06/ 
40cfr26__06.html [accessed 12 June 2007]. 

CIOMS (The Council for International Organizations of 
Medical Sciences) (2002). International Ethical Guidelines 
for Biomedical Research Involving Human Subjects. World 
Health Organization. Geneva, Switzerland. Available: 
http://www.cioms.ch/frame guidelines nov_2002.htm 

[accessed 12 June 2007], 

Diekema DS (2005) “Payments for Participation of Children 
in Research.” Chapter in: Kodish, E, Editor. Ethics and 
Research with Children: A Case-Based Approach. New 
York, NY: Oxford University Press. 143-160. 

Dickert N, Emanuel E, Grady C (2002). Paying research 
subjects: an analysis of current policies. Ann Intern Med 
136(5):368-373. 

Emanuel EJ (2004). Ending concerns about undue 
inducement. J Law Med Ethics 32(1): 100-105. 

Emanuel, EJ, Wendler D, Grady C (2000). What makes 
clinical research ethical? JAMA 283(20): 2701-2711. 


64 





Erlen JA, Sauder RJ, Mellors MP (1999). Incentives in 
research: ethical issues. Orthop Nurs 18(2):84-87. 

European Parliament (2001). On the approximation of the 
laws, regulations, and administrative provisions of the 
Member States relating to the implementation of good 
clinical practice in the conduct of clinical trials on medicinal 
products for human use. Directive 2001/20/EC Article 4(d) 
of the European Parliament and of the Council of 4 April 
2001 . 

Flory J, Emanuel E (2004). Interventions to improve research 
participants’ understanding in informed consent for 
research: a systematic review. JAMA 292( 13): 1593-1601. 

Fry CL, Ritter A. Baldwin S, Bowen KJ, Gardiner P, Holt T, 
Jenkinson R, Johnston J (2005). Paying research 
participants: a study of current practices in Australia. J Med 
Ethics 31:542-547. 

Grady, C (2005) Payment of clinical research subjects. J Clin 
Invest 115:1681-1687. 

Grady C, Dickert N, Jawetz T, Gensler G, Emanuel E (2005). 
An analysis of U.S. practices of paying research 
participants. Contemp Clin Trials 26:365-375. 

litis AS, DeVader S, Matsuo H (2006). Payments to children 
and adolescents enrolled in research: a pilot study. 

Pediatrics 118(4): 1546-1552. 

IOM (Institute of Medicine) (2004). Ethical Conduct of 
Clinical Research Involving Children. Marilyn J. Field and 
Richard E. Behrman (eds). Washington, DC: The National 
Academies Press. 

IOM (Institute of Medicine) (2002). Responsible Research: A 
Systems Approach to Protecting Research Participants. 
Daniel D. Federman, Kathi E. Hanna, and Laura Lyman 
Rodriguez (eds). Washington, DC: The National Academies 
Press. 

Menikoff J (2005). Of babies, bugs, and bombast: A look 
behind the crash-and-bum of the CHEERS pesticide study. 
Med Res Law Policy Rep 4( 14):586-512. 

NCS (National Children’s Study) (2007) Research Plan, 
Volume 1, Version 1.1, June 20, 2007. Available: 
www.nationalchildrensstudv.gov/research/research plan/upl 

oad/Research Plan Volume 1 .pdf [accessed 12 September 
2007.]. 

NIH (National Institutes of Health) (2005). Report and 
Recommendations on Public Trust in Clinical Research for 
the NIH Director from the Director’s Council oj Public 
Representatives (COPR). National Institutes of Health, 
Director’s Council of Public Representatives, January 14, 


2005. Available: http://copr.nih.gov/reports/public trust.asp 
[accessed 12 June 2007]. 

NRC (National Research Council) (2004) Research Priorities 
for Airborne Particulate Matter: IV. Continuing Research 
Progress. Washington, DC: The National Academies Press. 
Available: 

http://books.nap.edu/openbook.php7record id= 10957 

[accessed 16 August 2007]. 

NRC & IOM (National Research Council and Institute of 
Medicine) (2005). Ethical Considerations for Research on 
Housing-Related Health Hazards Involving Children. 
Washington, DC: The National Academies Press. Available: 
http://books.nap.edu/catalog.php7record id=l 1450 

[accessed 12 June 2007]. 

OMB (Office of Management and Budget). (2006a). Standards 
and Guidelines for Statistical Surveys. Section 2.3, Data 
Collection Methodology. 

http://www.whitehouse.gov/omb/inforeg/statpolicy/standard 

s stat surveys.pdf 

OMB (Office of Management and Budget). (2006b). 

Questions and Answers When Designing Surveys for 
Information Collection. Office of Information and 
Regulatory Affairs. January, 2006. 
http://www.whitehouse.gov/omb/inforeg/pmc survey guidanc 

e 2006.pdf 

Paasche-Orlow MK, Taylor HA, Brancati FL (2003). 
Readability standards for informed-consent forms as 
compared with actual readability. N Engl J Med 348(8):721- 
6 . 

Russell ML, Moralejo DG, Burgess ED. (2000). Paying 
research subjects: participants' perspectives. J Med Ethics 
26(2): 126-30. 

U.S. DHEW (U.S. Department of Health, Education, and 
Welfare) (1979). The Belmont Report: Ethical Principles 
and Guidelines for the Protection of Human Subjects of 
Research. Washington, D.C.: National Commission for the 
Protection of Human Subjects of Biomedical and 
Behavioral Research. Available: 

htt p://ohsr.od.nih. gov/guidelines/belmont.html [accessed 
June 2007]. 

U.S. FDA (U.S. Food and Drug Administration) (1998). 
Information Sheets: Guidance for Institutional Review 
Boards and Clinical Investigators 1998 Update. U.S. Food 
and Drug Administration, Washington, DC. Available: 
http://www.fda.gov/oc/ohrt/irbs/toc4.html [accessed May 
2007], 

U.S. HHS (U.S. Department of Health and Human Services) 
(1993). Protecting Human Research Subjects: Institutional 


65 














Review Board Guidebook. Office for Human Research 
Protections. Available: 

http://www.hhs.gov/ohrp/irb/irb guidebook.htm [accessed 
12 June 2007], 

VanderWalde A (2005). Undue inducement: the only 
objection to payment? Am J Bioethics 5(5):25-27. 


Weise KL, Smith ML, Maschke K.J, Copeland L (2002). 
National practices regarding payment to research subjects 
for participating in pediatric research. Pediatrics 
1 10(3):577-582. 

Wendler D, Rackoff JE, Emanuel EJ, Grady C (2002). The 
ethics of paying for children’s participation in research. J 
Pediatr 141(2): 166-171. 


66 



SECTION 6 


Building and Maintaining Appropriate Community and 

Stakeholder Relationships 


Community engagement promotes active 
community involvement in the processes that shape 
research strategies and the conduct of research studies. 
In developing this document, NERL held an expert panel 
workshop to identify the content and organization of this 
document (ERG, 2007). That panel of experts concluded 
that the need to engage the community in observational 
research was based on the ethical principles of (1) 
respect for persons, which manifests itself in both a 
respect for the individual and, through respect for the 
community, their culture; (2) fairness, resulting in efforts 
to assure equity in resources, burden, and benefits; and 
(3) beneficence, including “empowering the community 
to endure.” 

Involving the community in the research effort can 
improve the research both scientifically and ethically. In 
the document. Ethical Considerations for Research on 
Housing-Related Health Hazards Involving Children , 
the joint NRC-IOM committee found that community 
involvement was a “guiding theme” of their findings 
(NRC & IOM, 2005). Because the researchers were 
working in the homes and communities of the 
participants, they faced issues that were different from a 
clinical setting. They were challenged to think about the 
fundamental ethical principles in the context of the 
research setting and about how those ethical principles 
should be interpreted in that setting. “When researchers 
discuss a planned study with community representatives, 
understand their concerns and needs, and respond to 
them, protocols can be strengthened both scientifically 
and ethically” (p. xii, NRC & IOM, 2005). Just as was 
described in Section 5, where the informed consent 
process was described as needing to be “an on-going, 
interactive dialogue between research staff and research 
participants involving the disclosure and exchange of 
relevant information, discussion of that information, and 
assessment of the individual’s understanding of the 


discussion” (Recommendation 4.1, IOM, 2004), so, too, 
the process of community involvement should be a 
process of effective two-way communication. These 
NRC & IOM comments emphasize how critical 
effective, bidirectional communication is to the scientific 
and ethical foundation of a research study in such a 
setting. 

EPA has established a public involvement policy to 
“improve the content of the Agency’s decisions and 
enhance the deliberative process” (U.S. EPA, 2003) (see 
Text Box 6-1). The policy is focused largely on Agency 
decisionmaking processes (e.g., rulemaking, permit 
issuance. Superfund remediation, etc.), whereas observa¬ 
tional human exposure studies are intended to provide 
data to inform those decisionmaking efforts. 
Nonetheless, the Agency policy may be helpful in 
planning for community involvement in observational 
human exposure studies. The policy is intended to 
promote mutual trust and openness between EPA and the 
public, to improve the quality of the Agency’s actions, 
and to promote the public’s involvement in the Agency’s 
mission of promoting human health and the 
environment. The policy identifies seven basic steps for 
effective public involvement and offers guidance for 
implementing public involvement at EPA. 


Text Box 6-1. Seven Basic Steps for 
Public Involvement at EPA 

1. Plan and budget for public involvement activities. 

2. Identify the interested and affected public. 

3. Consider providing technical or financial assistance to 
facilitate involvement. 

4. Provide information and outreach to the public. 

5. Conduct public consultation and involvement activities. 

6. Review and use input, and provide feedback to the public. 

7. Evaluate public involvement activities . 


67 




6.1 Approaches to Community Involvement 

Community involvement can take many forms. The 
forms of community involvement are not mutually 
exclusive, and researchers may use several approaches 
for seeking community involvement. The nature and 
extent of community involvement reasonably would 
depend on the nature of the research itself and the 
affected community. In Section 2, the authors discussed 
some reasons for involving the community early in the 
research planning and scoping process and the benefits 
that community involvement may bring to the research 
effort. “Community residents can be involved in the 
research process as research staff, through community 
consultation and review, membership on community 
advisory boards, and involvement in a community-based 
participatory research process” if that is used (p. 83, 
NRC & IOM, 2005). In addition, IRBs may seek 
additional community representation on the IRB panel. 

The Centers for Disease Control and Prevention 
(CDC) recommends nine governing principles for 
engaging communities in health-related research (see 
Text Box 6-2). Health research is a “privileged and 
empowered activity in that the researchers have special 
access to resources and sensitive information about 
people and, through the analysis and presentation of 
findings, are able to influence the way people think and 
have considerable influence on decisions regarding the 
allocation of resources” (CDC, 1997). Regardless of the 
approach utilized to involve the community in research, 
whether the process employs community-based 
participatory research (CBPR) or another community 
engagement method, researchers should guide their 
interactions with community members using these 
underlying principles to promote the aforementioned 
ethical principles of respect of persons, fairness, and 
beneficence. 

One form of community involvement is to include 
qualified members of the community on the research 
staff. Section 2 advocates community representatives as 
part of the research team. Paid research staff members 
from the community could serve as valuable consultants 
for protocol development and research design, including 
how to collect the data, how to recruit and retain 
participants, and how to interpret and disseminate the 
results. However, including paid research staff from the 
community may introduce a conflict of interest among 
community members: community representatives may 
feel a greater allegiance to the researchers providing the 
payment and be less inclined to uphold the interests of 
the community. In addition, the community may come to 
view the paid research staff from the community as 


“outsiders.” To help alleviate these potential issues, 
researchers should ensure an equitable distribution of 
paid research work among different communities within 
the larger community as to not promote a perceived bias 
among community members. Additionally, when 
possible, researchers should make efforts to provide 
payments to community members employed as research 
staff through community partner organizations to 
prevent conflict of interest issues. Refer to Section 5 for 
further discussion on remuneration of community 
members as research participants. 


Text Box 6-2 

Community Engagement Principles for 
Researchers 

(From CDC, 1997) 

Requirement 

Explanation 

Clarity 

Clear communication of the study objectives, 
research goals, and the populations or 
communities of interest. 

Knowledge of 
the Community 

Familiarity with the economic conditions, 
political structures, demographics, history, past 
research experiences, and research perceptions 
of the community. 

Visibility 

Travel to the community, interact with formal 
and informal leadership, and establish 
relationships to build trust. 

Acceptance 

Acknowledge, without judging, the assets and 
deficits of the community. 

Partnership 

Balanced discussion and shared 
decisionmaking among participants concerning 
risks, responsibilities, expectations, benefits, 
and investment. 

Respect 

Value the diversity of culture, history, beliefs and 
opinions within the community for improved 
understanding. 

Asset Utilization 

Identify and mobilize community assets to 
improve scientific credibility of the interpretation 
and dissemination of results. 

Flexibility 

Anticipate changes within the community in 
regard to perceived benefits of research and 
stakeholder interest and additional time and 
resource needs. 

Commitment 

Prepare to engage the community beyond the 
constraints of the research projects, before and 
after, to promote longevity of the relationship for 
future research . 


Furthermore, institutional and community partners 
need to ensure that anyone involved as part of the 
research team has the requisite research and social skills. 
Researchers often place a greater emphasis on scientific 
over social skills and may, in turn, assume that they have 


68 

















the necessary expertise to conduct research in 
community settings. Likewise, research staff from the 
community should have knowledge of research 
fundamentals. Education and training targeted at both 
the institutional researcher and the community 
researcher may, respectively, improve the competence of 
researchers to work with communities and the scientific 
literacy of the public. 

A recent NERL study, the Detroit Exposure and 
Aerosol Research Study (DEARS), included community 
members as paid members of the research team. The 
community researchers were instrumental in recruiting 
study participants from the seven study neighborhoods 
in Detroit that required multiple door-to-door visits to 
the homes of potential participants to discuss the 
DEARS study. The success of DEARS was dependent 
on researchers developing strong relations with 
community leaders and State and local organizations. 

A second approach to community involvement is to 
seek community consultation and review. Researchers 
may periodically meet with community residents in a 
process of “engagement, dialogue, and feedback” (Dula, 
1994) to discuss research plans, research progress, and 
results. The objective is to seek a dialogue with 
community residents to promote co-learning and asset 
sharing between the researchers and the community. 
Effective communication—open, honest, jargon free—is 
imperative to the successful use of this approach. 
Effective communication ensures that the community 
has a voice in the research process for the expressed 
purpose of increasing the community’s trust and 
engagement in the research, the applicability of the 
research to the community’s needs, and the benefit of the 
research to the community. Authentic community 
consultation embraces the “experiential knowledge of 
the average citizen” (Leung et al., 2004). When 
developing research budgets and timescales, researchers 
who plan to incorporate community consultation and 
review in the research process should take into account 
the additional expenses and time necessary for 
community marketing efforts and travel. 

Corbum (2002) describes a successful community 
participation in an EPA exposure assessment in 
Brooklyn, NY. He explains how a shift of focus from 
risk assessment to exposure assessment may provide an 
opportunity for community engagement to improve the 
technical assessment. Listed among the specific factors 
integral to the assessment’s success are the incorporation 
of local, nonexpert information by community groups 
during the consultation and review process that was used 
to modify the conventional risk assessment process and 


the inclusion of community-based organizations on the 
scientific research team as contributors to the data 
collection, modeling, and interpretation processes, where 
they provided data and expertise not available through 
traditional research frameworks (Corburn, 2002). 

Community advisory boards (CABs) also have been 
used as an approach for getting the community involved 
in the research effort. A CAB could be formed to serve 
as a liaison between participants and researchers. In 
particular, CABs can advise the researchers about 
community concerns and assist in the development of 
materials to explain the study to potential participants. 
CABs should be sufficiently large to ensure a diversity 
of community views, perspectives, and attitudes. 
Representatives from the board may be selected for 
participation on the research team. In Section 5, it was 
noted by the authors that such a board could function as 
an oversight committee in case of any participant 
grievances. According to Quinn (2004), the success of 
CABs “lies in the ability of the researchers and CABs to 
form a true partnership, enabling their different voices to 
be heard equally.” Creating a CAB may be perceived as 
“window dressing” and, in fact, harm relationships with 
the community if researchers are not truly open to 
working with the CAB. 

O’Fallon and Dearry (2002) describe how the Tribal 
Efforts Against Lead (TEAL) partnership collaborated 
with EPA to clean up and minimize exposure to toxins 
from a Superfund site in Ottowa County, OK. The 
TEAL project utilized the services of a CAB, which 
included representatives from several local tribes, to 
ensure that the research would be responsive to the needs 
and concerns of the tribal residents. The CAB facilitated 
the researchers interactions with the target communities 
“by helping the investigators interpret data and distribute 
information to the communities” and “developing and 
conducting the training” of the community members on 
risk reduction strategies. The value of the research to the 
TEAL target communities would have been diminished 
had a CAB not been formed to assist the researchers 
with specific best practices to use when engaging the 
tribal members and the appropriate tribal leadership 
structures. 

Another potential approach to involve the 
community is to use a CBPR approach, wherein the 
community is actively involved in each step of the 
research process, including sharing of decisionmaking 
power and resources. This will impact decisions about 
study design, study methods, dissemination of findings, 
and resulting actions. “Under the principles of 
community-based participatory research, research must 


69 



address the concerns, needs, and priorities of the 
communities where it is conducted and lead to actions 
and changes that benefit the community” (p. 86, NRC & 
IOM, 2005). Information about CBPR approaches can 
be found online at the HHS Web sites 
http://www.ahrq.gov/clinic/epcsums/cbprsum.htm and 
http://www.ahrq.gov/research/cbprrole.htm . 

Israel et al. (2005a) reviewed the results of CBPR 
efforts at six Children’s Centers co-funded by EPA and 
the National Institute of Environment Health Sciences. 
They found that considerable commitment of resources 
and time are needed for the approach to be successful, 
and the translation of research findings into interventions 
and policies is of the utmost importance. Community 
partners played little role in defining the research topics 
and data analysis, but were vital to disseminating the 
findings to the community. Keeler et al. (2002) describe 
using CBPR methods to evaluate personal and 
community-level exposures to particulate matter among 
asthmatic children in Detroit. The research partnership, 
Community Action Against Asthma (CAAA), consisted 
of representatives from local health organizations, 
community environmental advocacy groups, State and 
local governmental agencies, and academia. The CAAA 
partnership credits community involvement as active 
research partners in the research process with the success 
of the project to acquire “more relevant exposure data 
for the study of children in urban neighborhoods” and to 
provide “immediate knowledge and understanding of the 
outcomes and results of the combined environmental 
health analysis to the communities” (Keeler et al., 2002). 

There are, however, several drawbacks to utilizing 
CBPR methods that researchers should consider before 
developing a CBPR project. CBPR is time consuming 
(develop partnership, establish and agree on research 
aims and objectives, disseminate results to the 
community using appropriate methods, and review 
manuscripts and presentations) and not conducive to 
situations where rapid decisions are necessary given a 
tight timeline. Weighing the research need versus the 
community’s desire for an intervention is the greatest 
source of tension in conducting CBPR (Israel et al., 
2005b). 

One additional opportunity for community input 
may involve participation on an IRB. IRBs are required 
by the Common Rule to have members who are sensitive 
to “community attitudes” [40 CFR 26.107(a)], How they 
meet this obligation is totally at their discretion, and 
NERL researchers have no influence. There have been a 
number of recent articles in the literature about IRBs that 
have envisioned a need for more regulatory reform 


(Ledford, 2007). Ideally, the IRB should take into 
account the views of the community. Quinn (2004) 
argues for extending protections now reserved for 
individuals to groups (populations and communities) 
through CABs. Her argument is that there are “ethical 
issues related to research with communities that are 
distinctly different from the ethical issues related to 
research with individuals.” CAB members have to be 
educated on human subjects’ protections, should 
represent their communities honestly, and need to be 
willing to interact with researchers on complex research 
issues. 

Gilbert (2006) goes even further. He suggests 
supplementing or even replacing traditional IRBs with 
environmental health and community review boards 
(EHCRBs). He argues that traditional IRBs are 
inadequate for the review of community-based research 
because they were developed to address issues related to 
individuals involved in research projects, not 
communities. He proposes EHCRBs that combine the 
fundamental and ethical concept of traditional IRBs with 
an expanded ethical construct of dignity, veracity, 
sustainability, and justice, with added emphasis on 
community. He envisions that an EHCRB would 
function as an IRB with the requirements and 
responsibilities for review for the protection of human 
subjects, plus the additional role for review of 
community issues associated with the research project. 

Gilbert’s recommendation for EHCRBs is consistent 
with the recommendations of the authors of the NRC & 
IOM report who recommended that “Institutional review 
boards that review housing health hazards research 
involving children should ensure that those boards have 
the necessary expertise to conduct a complete and 
adequate review, including expertise on research 
involving children and community perspectives” (NRC 
& IOM, 2005). 

Involving community representatives in the IRB 
process is challenging for IRBs, however. One challenge 
could be the need to provide sufficient training to 
community members about the IRB process and the 
regulations governing IRBs. This can be significant if 
members sit on an IRB for a limited time to review 
specific community-based studies. In some cases, IRBs 
may invite community members to participate in the IRB 
process as nonvoting members to solicit the community 
perspective. This approach, which would be totally at the 
discretion of the IRB, might reduce the burden on the 
community representative by reducing training 
requirements. 


70 




6.2 Issues in Community Involvement 

There are a number of issues that need to be 
addressed in any efforts to ensure community 
involvement. The Expert Panel that was convened to 
advise NERL about scientific and ethical issues in 
observational human exposure studies discussed a 
number of challenges (ERG, 2007). The topics that the 
expert panel identified as issues are discussed below. 

6.2.1 Defining “Community” 

“Community” refers to a group of people united by a 
shared attribute, and the attributes can be wide-ranging, 
such as geography, culture, social characteristics, values, 
interests, traditions, or experiences (ERG, 2007). 
Community can be defined broadly (as a system of 
interrelated groups operating to meet the needs of its 
members) or more narrowly (as the population from 
which study participants are selected). For observational 
field studies, the Expert Panel from the workshop 
suggested the narrow definition. A narrow definition 
allows social and cultural factors to be included but 
excludes government agencies, industry, and others who 
do not necessarily represent the interests of the 
participants (ERG, 2007). 

Central to the definition of a community is a sense 
of “who is included and who is excluded from 
membership” (NRC & IOM, 2005). A person may be a 
member of a community by choice, as with voluntary 
associations, or by virtue of their innate personal 
characteristics, such as age, gender, race, or ethnicity 
(NRC & IOM, 2005). As a result, individuals may 
belong to multiple communities at any one time. When 
initiating community engagement efforts, one should be 
aware of these complex associations in deciding which 
individuals to work with in the targeted community. 

Quandt et al. (2001) discuss a CBPR research 
project, Preventing Agricultural Chemical Exposure in 
North Carolina Farmworkers, where the process of 
defining a community was complicated by language, 
ethnic and racial stereotypes, and lack of organization. 
Many of the affected farmworkers originated outside the 
United States from several different Spanish-speaking 
countries and possessed contradicting viewpoints on 
research and the utility of community organization. 
Moreover, the community organization tailored for this 
farmworker demographic did not include enough 
members to adequately populate the study. The 
researchers utilized multiple approaches, including 
community forums, community advisory councils, and 
public presentations, to identify a diverse, yet viable, 
community within the broader farmworker population. 


Through this process of using multiple participatory 
strategies to define the community, a sense of 
community was nurtured among the farmworkers 
collectively (O’Fallon and Dearry, 2002). 

Understanding and describing a community (CDC, 
1997) involves exploring factors related to 

• people (including socioeconomics and demographics, 
health status, and cultural and ethnic characteristics), 

• location (geographic boundaries), 

• commonalities (including shared values, interests, and 
motivating forces), and 

• power relationships (including formal and informal 
lines of authority and influence, stakeholder 
relationships, and resource flows). 

It is important to distinguish between stakeholders 
and the community, but both should be engaged at some 
point in the course of a study. Stakeholders are groups or 
organizations that may affect, be affected by, or perceive 
themselves to be affected by a decision or activity. 
Stakeholders may have a direct or indirect interest in the 
“matter” of interest. They may include individuals; 
environmental, social, or community nongovernment 
organizations (NGOs); government entities; businesses; 
and industry. Stakeholders include business, industry, 
and various levels of government. A critical difference 
between the community and stakeholders is that the 
community has a right to speak for its own interests, but 
stakeholders cannot represent or speak for the 
community. Although relationships with stakeholders 
can, at times, be confrontational, stakeholders often 
provide useful information and expertise. When 
stakeholders and the community members overlap in 
particular individuals, it is important to distinguish the 
role in which the individual is acting (ERG, 2007). 

6.2.2 Identifying Who Represents the 
Community 

To sufficiently represent the community, an 
individual has to have not only the right to speak for the 
community’s interests (a right afforded by legitimate 
membership in the group) but also should be able to 
describe those interests on behalf of the community. 
Identifying those who represent the community is not 
simply a matter of identifying the most vocal activists 
because those individuals do not necessarily represent 
the interests of the entire community. In fact, several 
individuals may be necessary to adequately represent the 
diversity of viewpoints within a community; in such 
cases, a CAB may be appropriate (ERG, 2007). One of 
the researcher’s first steps should be asking the potential 
participants from the community who they see as a 


71 


1 


legitimate representative (i.e., someone who can speak 
for them). Corbum cites an example of a locale in 
Brooklyn, NY, that contained individuals with widely 
different backgrounds. It was impossible to identify 
appropriate spokespeople, or even to define the nature of 
the community, without talking with community 
members (Corbum, 2007). 

The NRC & IOM (2005) Report also discusses the 
issue of who can represent the identified community. 
Some communities may have a formal governmental 
stmcture and a recognized political authority (e.g., 
Native American tribes). Other communities may have 
clearly identifiable leaders (e.g., religious communities), 
whereas still other communities have no formal 
leadership stmcture at all. Whether there is a legitimate 
political authority or some other hierarchal leadership 
stmcture, the goal is to seek community input as to who 
best represents the interests of the community with 
regard to the proposed research project, rather than 
selecting those who are favorable to the research project. 
The NRC & IOM report cautions against the ethically 
questionable practice of seeking out population 
spokespeople and research participants whose positive 
response to a research plan can be predicted in advance 
and refers the reader to an article on this topic by Juengst 
( 2000 ). 

With multiple sources of leadership and authority in 
many communities, careful consideration should be 
given to what aspect of the community a particular 
person will represent, and what efforts may be needed to 
ensure that the entire range of views in a community are 
obtained. Researchers should consider reaching out to 
multiple organizations such as churches, social service 
agencies, community-based organizations, and tenant 
and other community advocacy groups. 

6.2.3 Building Relationships and Trust 

A key first step in developing tmst is to establish a 
relationship with the community before the study. Tmst 
must be built; it cannot be assumed. This relationship 
involves not only listening to community input but 
actually taking it into consideration (ERG, 2007). A long 
history of research with no direct benefits and no 
feedback of results to the community, however, has 
contributed to a general mistmst of researchers by 
community members (Israel et al., 1998). Moreover, the 
recurring abuse of tmst in communities is a reality that 
researchers should be aware of when attempting to build 
a long-term relationship (Minkler and Wallerstein, 
2003). Past ethical failures have created distrust among 
some communities and have produced great challenges 


for current community organizers. Although it may seem 
self-evident, researchers need to remember that ethical 
action, during all phases of the research, is necessary for 
developing and maintaining the tmst of communities 
(Perkins and Wandersman, 1990; CDC, 1997). 

Developing trust is a difficult and time-consuming 
process. Israel et al. (2005b) suggest a number of ways 
partners can gain each other’s tmst. First, partners can 
show respect by seriously considering the ideas and 
opinions of others. Second, trustworthiness can be 
demonstrated by following through with those things 
that each partner commits to. Third, partners have to 
respect confidentiality. Fourth, they recommend 
attending to each other’s interests and needs by 
participating in activities beyond the specific work of the 
partnership. 23 A history of prior positive working 
relationships is also beneficial (Israel et al., 1998). 

Tmst cannot be separated from respect. Potential 
participants need to see researchers fostering respect for 
community members and leaders to gain tmst. For 
example, meeting with key community leaders and 
groups in their surroundings helps to build tmst for a 
true partnership. Such meetings provide organizers of 
engagement activities with more information about the 
community, its concerns, and factors that will facilitate 
and constrain participation. Once a successful rapport is 
established, the meetings and exchanges with 
community members can become an ongoing and 
substantive partnership (ERG, 2007). 

One mechanism for helping to build tmst may be a 
contract with the community. A community contract 
outlines the roles and expectations of both the researcher 
and the community. Fiving up to these agreements 
builds tmst with all partners, and the establishment of 
the agreement helps reduce misunderstandings. 
Contracts or memorandums of understanding that outline 
the roles and expectations of the researcher and the 
community are discussed in both Minkler and 
Wallerstein (2003) and Israel et al. (2005b). An example 
outlining expectations in a partnership with tribal 
communities is presented in Appendix E of Minkler and 
Wallerstein (2003), whereas an example discussing 
access to data and authorship issues is presented in 
Appendix I of Israel et al. (2005b). An example of a 
memorandum of understanding between the University 
of Michigan School of Public Health, Detroiter’s 
Working for Environmental Justice, the Detroit Hispanic 


3 For a more detailed description of each of the suggestions 
for enhancing trust, please see Chapter 3 of Israel et al. (2005). 


72 



Development Corporation, and the Warren Conner 
Development Coalition for a study investigating asthma 
is available at http://depts.washington.edu/ccph/pdf files 
/MOUlO.pdf . 

Work within communities involves a considerable 
investment of researchers’ and residents’ time. It should 
be an ongoing, interactive exchange of information and 
ideas between the researchers and the community 
members, where voices are both heard and honored. 
Trust is fostered when all interested parties feel that they 
have influence, and that their input contributes to the 
community effort. The collaborations should be 
inclusive of the entire community, including those 
members with incompatible, interests and perceptions. If 
participation, influence, and benefits are limited only to 
some of the partners, then distrust is likely, and the 
potential benefits of community involvement may be 
lost. Being inclusive can create some organizing 
challenges, but the benefit of effective community 
involvement “has the potential to lead to greater 
understanding of community perspectives of the risk and 
benefits of research, improve informed consent, increase 
study enrollment, enhance data validity and quality, and 
build trust for research” (NRC & IOM, 2005). 

6.2.4 Importance of Language and 
Communications with the Community 

Even when all partners and community members are 
speaking the same language, some terms are not 
necessarily understood by all. Communications with 
participants should be reviewed by all partners to ensure 
that the language used will be appropriate for all 
participants. At times, one method to communicate 
research findings will not fit all community members 
and partners. Even among the partners, understanding 
each other’s meanings is essential, so that all partners 
can move forward with a common understanding (Israel 
et al., 2005b). 

Furthermore, Minkler and Wallerstein (2003) note 
that “research must be produced, interpreted, and 
disseminated to community members in clear, useful, 
and respectful language.” Researchers, and especially 
researchers in a government agency, may have their own 
distinct lexicon. Researchers should be careful to avoid 
acronyms, jargon, or technical terms that may obscure 
the meaning or intimidate participants who are not 
familiar with the terms. Communicating in “plain 
language” to “explain the research in an honest, 
straightforward way” will help build a strong 
relationship with the community and the participants and 


also help enhance public trust (Recommendation 11, 
NIH, 2005). 

Culturally sensitive communication is necessary to 
developing effective research partnerships with 
communities. To develop effective communications, 
researchers must understand key aspects of the cultures 
influencing the intended audience and build that 
understanding into the communication strategy (Tillman, 
2002). The symbols, metaphors, visuals (including 
clothing, jewelry, and hairstyles), types of actors, 
language, and music used in communication materials 
all convey culture. Discussions with community 
members can assist researchers in identifying messages 
and images that resonate across groups or suggesting 
situations in which different messages or images are 
likely to work best. 

As discussed above and in Sections 5 and 7, 
communication materials must be tailored for each 
individual community and must be written in a language 
and at a reading level that will ensure comprehension. 
Many IRBs require materials to be prepared at a 5th 
grade reading level. Researchers should evaluate the 
reading level of all data collection instruments and study 
communication materials and should objectively 
measure comprehension in pretests prior to use in the 
study. Similarly, if translations of materials are required, 
certified translating services should be used to ensure 
accuracy and comprehension. 

6.2.5 Recognizing and Addressing 
Cultural Differences 

Building and maintaining appropriate community 
and stakeholder relationships requires acknowledgment 
of the diversity within communities with regard to many 
factors, including, but not limited to, race/ethnicity, 
religious beliefs, heritage, and lifestyles. Different 
groups in the study area may have different cultural 
norms and practices. The researchers should take these 
issues into consideration as they work in the community. 
Community partners can help researchers design the 
study to be attentive to the increasing heterogeneity of 
community groups (Minkler and Wallerstein, 2003, 
Chapter 4) and to the different boundaries of privacy 
(crucial when designing sampling strategies) of different 
groups (Israel et al., 2005b, Chapter 11). 

Vega (1992) provides a thorough discussion of the 
theoretical and pragmatic implications of cultural 
diversity for community research and explains that 
researchers should interact with communities using 
methods that promote understanding and demonstrate 
sensitivity and competence in working with diverse 


73 




1 


cultures (e.g., with respect to class, gender, ethnicity, 
race, age, and sexual orientation). To aid in this process, 
researchers should include sufficient time in their project 
timeline to interact and dialogue with the community 
before the study begins to understand the cultural issues 
that may affect the research. Researchers and the results 
of their work are expected to promote a strengthening of 
the community; however, it should be recognized that, 
given the heterogeneity and the diverse views within a 
community, the study findings potentially may conflict 
with the desires of the community or may promote 
feelings of anger or distrust among members of the 
community with each other. Enlisting the services of a 
third-party evaluator/mediator may be useful for 
sustaining positive relations between all research 
participants and the community at large. 

The Research Triangle Park Particulate Matter Panel 
Study (Williams et al., 2003), a NERL investigation of 
PM and related pollutants involving African-Americans 
in North Carolina, demonstrated an effective strategy for 
using communication to address cultural differences 
between the community and research personnel. Before 
beginning the research, the study design included time 
and a budget for building collaborations with 
organizations having close ties with the African- 
American community to establish trust between the 
community and research team. Using input from the 
community partner organizations, the researchers 
developed a systematic communication plan to establish 
rapport with the community and to guide interaction 
between study participants and the key study personnel. 
A well-designed and culturally sensitive communication 
plan was integral to the success of the study. Eighty 
percent of the original participants completed the four- 
season study (Williams et ah, 2003). 

6.2.6 Honesty, Power Relationships, and 
Partnerships 

The NRC & IOM report (NRC & IOM, 2005) 
describes a relational paradigm that acknowledges that 
research is part of a broader societal context, with the 
conduct of research often mirroring a system in which 
power is unequally and perhaps unfairly distributed. The 
trust and mutual commitment required from the 
researchers and the community are subject to the overall 
power relations in society. 24 The Expert Panel convened 
to discuss the content of this document recognized that 


24 A discussion of the evolution of theories on power relations, including the 
contribution of feminism, poststructuralism, and postcolonialism, can be 
found in Minker and Wallerstein (2003, Chapter 2). 


the researchers have a variety of forms of power that 
needed to be understood and acted on ethically (ERG, 
2007). One form of power is resources, both funds and 
access to resources and decisionmakers. Other forms of 
power may be more subtle, including expertise, which 
can intimidate or limit a participant’s choices. Peer 
pressure, fear of intimidation, expectations of benefits 
from the research, and power to stigmatize the 
community all, whether real or perceived, can influence 
the relationship between the researcher and the 
community. Many forms of power may be tipped toward 
the researcher, but the community often has power in the 
form of knowledge about the community that can impact 
the quality of the research effort. An ethical balance of 
power can lead to benefits for all partners (ERG, 2007). 

In describing principles in Methods in Community- 
Based Participatory’ Research for Health , Israel et al. 
(2005b) describe CBPR as facilitating “a collaborative, 
equitable partnership in all phases of research, involving 
an empowering and power-sharing process that attends 
to social inequalities.” One way to address the inequities 
is to ensure that the roles and responsibilities are 
mutually acceptable to all parties. Researchers involved 
in CBPR should recognize and address the inequalities, 
thereby promoting trust, mutual respect, open 
communication, information sharing, collaborative 
decisionmaking, and resource sharing. 

It is important that researchers recognize that 
partnerships with the community are ongoing processes 
that need to be monitored and maintained. As a study 
progresses, the dynamics of the partnership may change 
as roles and responsibilities for the partners change. All 
partners need to be willing to make the investment of 
time and resources necessary to maintain an effective 
partnership. 

6.2.7 Building a Lasting Infrastructure 

Infrastructure is anything that builds the capacity of 
the community by providing its members with skills and 
resources. Infrastructure building ideally occurs 
throughout the project and should be included in the 
overall plan (ERG, 2007). When involving the 
community in the planning process, investigators need to 
be forthright regarding funding limitations and research 
expectations, such as publication and dissemination of 
results. The community needs to be made aware of the 
ephemeral nature of funding, even if it results in 
apprehension toward involvement. 

Researchers should communicate early on those 
issues that will become important once the research has 
been completed, such as sustainability. Frankness is 


74 



required to cultivate the community’s confidence and 
expertise over time. Because so much time and 
investment is involved in building an appropriate 
relationship with the community, researchers may wish 
to continue their relationship with the community even 
after the study has ended. Researchers should remain 
accessible for technical support related to the subject of 
the research. Helping community members identify new 
funding opportunities and assisting with the writing of 
grant applications are two examples of potential 
continued relationships. Many private sponsoring 
institutions already recognize the importance of enduring 
commitment and have used a variety of approaches, 
often involving funding, to ensure that these 
relationships are able to continue (ERG, 2007). The 
challenge will be for universities and Federal agencies to 
be able to establish similar funding mechanisms. 

The objective of capacity building is to involve 
members of the community in certain roles (e.g., 
performing interventions), training them to perform 
some of the functions initially performed by the research 
team. Certain research grants specifically support this 
type of training. Training can be reciprocal, and allowing 
the community to train the researchers (for example, in 
cultural sensitivity) not only fosters respect but also can 
lead to important new understanding. 

Another important step is to formalize the 
relationship between the community and the institution 
conducting or sponsoring the research, not just between 
the community and the individual researcher. 
Institutional relationships can survive even if individual 
researchers leave. Institutions may be reluctant to build 
enduring relationships with communities if they do not 
see long-term financial value in this investment. 
Researchers may be able to get more support from their 
institutions if they can document their successes (ERG, 
2007). 

6.3 Community Involvement in 
Observational Human Exposure Studies 

Observational human exposure studies, like those 
conducted by NERL, benefit from community 
involvement. Scientific rigor apart from ethical 
considerations fails as good science. Community 
involvement in research ensures that ethical standards 
are a priority in the study design and are pursued by the 
researchers throughout the study. The lorm and extent of 
community involvement will vary, depending on the 
scope and utility of the research effort. The nature of the 
community—the population from which the participants 
are selected—often will vary considerably from one 


study to the next, ranging from a small group involved in 
a pilot study to a randomized, representative sample of 
the whole population. As a result, the nature of the 
community involvement also will depend on the 
particulars of the study. The typical lack of direct benefit 
from observational human exposure studies may mean 
that many research efforts cannot meet all of the 
principles of CBPR. Nonetheless, community 
involvement should be included in observational human 
exposure research efforts to the fullest extent possible. 
As the NRC & IOM committee observes (p. 98, NRC & 
IOM, 2005): 

Community involvement, though time and resource 
intensive, is a necessary and useful component of... 
research with the potential to enhance trust and 
increase the relevance of research to affected 
communities. Thus, attention to the issues raised by 
the community and consideration of the most 
appropriate method of community involvement for a 
given research project is warranted. 

NERL researchers also should consider the 
recommendations set forth in the NRC & IOM report 
(Recommendation 5.1, p. 98, NRC & IOM, 2005) as 
they develop their research plans and protocol. 

Researchers...should describe in their protocols and 
IRB submissions how they have involved and will 
continue to involve the affected community in the 
research project, justify the lack of such involvement, 
and report how they have responded to any 
community concerns. 

Researchers and the members of the communities in 
which they work should recognize, however that the 
primary role of the researcher is to be an advocate for the 
science, not an advocate for the community. Although 
being an advocate for the community is desirable, and in 
many projects achievable, it should be recognized that 
resource constraints and potential conflicts of interest 
may impact the researcher’s ability to advocate for the 
community, particularly if it involves regulatory 
activities of the Agency. 

6.4 Identifying and Interacting with 
Other Stakeholders 

Like community involvement, stakeholder 
involvement in a research study can take many forms. 
Also like community involvement, researchers should 
engage stakeholders in their studies early in the planning 
stages. The relationship between the researchers and 
various stakeholders should be maintained during the 
study. How this relationship is maintained can be 
expected to vary with different stakeholders and may 


75 


( 


change as the study progresses. Stakeholders can provide 
useful information and perspective during the planning 
and implementation of observational human exposure 
studies. 

Stakeholders may include individuals, NGOs, 
businesses, industry, and various government entities or 
agencies with jurisdiction over or interest in the 
community. Stakeholders are a separate entity apart from 
the community, although they may conduct business or 
operate within the community or have a direct or indirect 
interest in the community’s activities. Even though they 
are not able to speak for the community, stakeholders 
may have knowledge of impacts and ideas about how to 
interpret and use the results of proposed research studies. 
Such knowledge may prove very helpful as part of the 
research planning and scoping (ERG, 2007). Including a 
variety of stakeholders in the planning process provides 
insight that comes from reconciling the disparate 
perspectives of different stakeholders. 

Observational human exposure studies conducted or 
supported by NERL may have many potential 
stakeholders, both internally in EPA and outside of the 
Agency. Internal stakeholders include the ORD Office of 
the Science Advisor, the Office of Science Policy, other 
laboratories and centers in ORD that may be interested 
in the study and its results, program offices, and the 
regional offices. Outside of the Agency, other Federal, 
State, and local agencies may be stakeholders. For 
example, CDC may be interested in biomonitoring 
studies. State agencies will be stakeholders when 
research is done in their state. Examples of NGOs that 
may be external stakeholders include the Natural 
Resources Defense Council, Environmental Defense, 
American Lung Association, American Academy of 
Pediatrics, American Chemistry Council, and literally 
hundreds of other organizations with interests in 
environmental or public health issues. Researchers 
should identify potential stakeholders and communicate 
with them early in the planning stages of a study if they 
are determined to be appropriate. Identifying the 
appropriate stakeholders who have a legitimate interest 
in the study will be done on a study-by-study basis and 
should be done in consultation with the research team, 
the community representatives, and senior management. 
In EPA, the Office of Public Affairs can assist in 
identifying contacts in stakeholder groups. 

The concept of “stakeholder” has been discussed in 
management literature since the 1980s. Mitchell et al. 
(1997) have developed an approach for identifying the 
relevant stakeholders through an assessment of their 
power, legitimacy, and urgency. Such an approach may 


be useful for identifying stakeholders to be involved in 
the research studies. In describing CBPR, Israel et al. 
(2005b) discuss the need to examine the advantages and 
disadvantages of extending membership beyond the 
“community of identity” at the outset. For example, they 
discuss the relative merits of including representatives of 
the agricultural industry in a study of farmworkers 
because of industry’s possible role in policy change and 
weigh their inclusion against the concerns that the true 
voice of the farmworkers may not be heard under such 
conditions. They also describe a possible solution of 
creating separate partnership groups. O’Fallon and 
Dearry (2002) explain the benefits of including diverse 
stakeholders for the dissemination of results. 

Successful interactions with stakeholders will 
require effective communication strategies and 
materials, as is discussed in the following section. After 
relevant stakeholders have been identified, they should 
be contacted to inform them of the proposed research 
study and to determine their interest in the study. If the 
stakeholders express an interest in participating, the 
research team should develop a plan for interacting with 
the stakeholders that includes roles and responsibilities, 
activities, and timelines that are mutually agreeable to 
the team, community representatives, and the 
stakeholders. There needs to be a clear agreement on the 
plan with all parties involved. Failure to have such an 
agreement may lead to misunderstandings of the roles of 
the stakeholders. As planning for the study proceeds, the 
plan for stakeholder involvement should be updated to 
reflect activities and timelines for longer term 
engagement. 

When developing relationships with stakeholders, 
researchers also should ensure that participation of the 
stakeholder in the study, regardless of level of 
participation, does not result in actual or perceived 
conflicts of interest. This should be addressed in the plan 
and agreement for stakeholder involvement. 

References 

CDC (Centers for Disease Control and Prevention) (1997). 
Principles of Community Engagement. ATSDR Committee 
on Community Engagement. Available: 
http://www.cdc.gov/phppo/pce/ [Accessed Oct. 2007], 

Corbum J (2007). Community knowledge in environmental 
health science: co-producing policy expertise. Environ Sci 
Policy 10(2): 150-161. 

Corbum J (2002). Environmental justice, local knowledge, 
and risk: the discourse of a community-based cumulative 
exposure assessment. Environ Mngt 29(4):451-466. 


76 



Dula A (1994). African American suspicion of the healthcare 
system is justified: What can we do about it? Camb Q 
Healthc Ethic 3(3):347-357. 

ERG (Eastern Research Group) (2007). Report on the 
Workshop to Discuss State-of-the-Science Approaches for 
Observational Exposure Measurement Studies. Held in 
Durham, North Carolina on November 28-29, 2006. Final 
Report: January 25, 2007. (PB2007-108905). 

Gilbert SG (2006). Supplementing the traditional institutional 
review board with an environmental health and community 
review board. Environ Health Perspect 114(10): 1626-9. 

10M (Institute of Medicine) (2004). Ethical Conduct of 
Clinical Research Involving Children. Marilyn J. Field and 
Richard E. Behrman (eds). Washington, DC: The National 
Academies Press. 

Israel BA, Parker EA, Rowe Z, Salvatore A, Minkler M, 

Lopez J, Butz A, Mosley A, Coates L, Lambert G, Potito 
PA, Brenner B, Rivera M, Romero H, Thompson B, 
Coronado G, Halstead S (2005a). Community-based 
participatory research: lessons learned from the Centers for 
Children's Environmental Health and Disease Prevention 
Research. Environ Health Perspect 113(10): 1463-71. 

Israel BA, Eng E, Schulz AJ, Parker EA (eds) (2005b). 
Methods in Community-Based Participatory Research for 
Health. San Francisco, CA: Jossey-Bass. 

Israel BA, Schulz AJ, Parker EA, Becker AB (1998). Review 
of community-based research: assessing partnership 
approaches to improve public health. Annu Rev Public 
Health 19:173-202. 

Juengst ET (2000). Commentary: What “community review” 
can and cannot do. J Law Med Ethics 28( l):52-54. 

Keeler G, Dvonch T, Yip F, Parker E, Israel B, Marsik F, 
Morishita M, Barres J, Robins T, Caldwell W, Sam M 
(2002). Assessment of personal and community-level 
exposures to particulate matter among children with asthma 
in Detroit, MI, as part of Community Action Against 
Asthma. Environ Health Perspec 110(Suppl 2): 173-181. 

Ledford H (2007). Human Subject Research: Trial and Error. 
Nature 448(7153): 530-532. 

Leung MW, Yen IH, Minkler M (2004). Community-based 
Participatory Research: a promising approach for increasing 
epidemiology’s relevance in the 21 st century. Int J 
Epidemiol 33(3):499-506. 

Minkler M, Wallerstein N (eds) (2003). Community-Based 
Participatory Research for Health. San Francisco, CA: 
Jossey-Bass. 


Mitchell RK, Agle BR, Wood DJ (1997). Toward a theory of 
stakeholder identification and salience: defining the 
principle of who and what really counts. Acad Manage Rev 
22(4):853-886. 

NIH (National Institutes of Health) (2005). Report and 
Recommendations on Public Trust in Clinical Research for 
the NIH Director from the Director’s Council of Public 
Representatives (COPR). National Institutes of Health, 
Director’s Council of Public Representatives, January 14, 
2005. Available: http://copr.nih.uov/reports/public trust.asp 
[accessed June 2007], 

NRC & IOM (National Research Council and Institute of 
Medicine) (2005). Ethical Considerations for Research on 
Housing-Related Health Hazards Involving Children. 
Washington, DC: The National Academies Press. Available: 
http://books.nap.edu/catalou.php7record id= 11450 

[accessed 12 June 2007], 

O’Fallon LR, Dearry A (2002). Community-based partici¬ 
patory research as a tool to advance environmental health 
sciences. Environ Health Perspect 110 Suppl 2:155-9. 

Perkins DD, Wandersman A (1990). You’ll have to work to 
overcome our suspicions: the benefits and pitfalls of 
research with community organizations. Soc Policy 
21(1 ):32-41. 

Quandt S, Arcury T, Pell A (2001). Something for everyone? 
A community and academic partnership to address 
farmworker pesticide exposure in North Carolina. Environ 
Health Perspect 109 Suppl 3:435-441. 

Quinn SC (2004). Ethics in public health research: protecting 
human subjects: the role of community advisory boards. Am 
J Public Health 94(6):918-22. 

Tillman, L. (2002). Culturally sensitive research approaches: 
an African-American perspective. Educ Researcher 31 (9):3-12. 

U.S. EPA (U.S. Environmental Protection Agency) (2003). 
Public Involvement Policy of the U.S. Environmental 
Protection Agency. EPA 233-B-03-022. Available: 
http://www.epa.uov/publicinvolvement/pdf/policv2003.pdf 

[Accessed 26 Sep 2007]. 

Vega WA (1992). Theoretical and pragmatic implications of 
cultural diversity for community research. Am J Commun 
Psychol 20(3):375-91 

Williams R, Suggs J, Rea A, Leovic K, Vette A, Croghan C, 
Sheldon L, Rodes C, Thornburg J, Eijire A, Herbst M, 
Sanders W (2003). The Research Triangle Park particulate 
matter panel study: PM mass concentration relationships. 
Atmos Environ 37:5349-5363. 


77 





Additional Information Resources 

Blumenthal DS (2006). A community coalition board creates a 
set of values for community-based research. Prev Chronic 
Dis 3(1): 1-7. Available: 

http://www.cdc.gov/pcd/issues/2006/ian/pdf/Q5 0068.pdf 

[accessed 12 June 2007]. 

Coleman CH, Menikoff JA, Goldner JA, Dubler NN (2005). 
The Ethics and Regulation of Research with Human 
Subjects. Newark: LexisNexis. 

Davies EF (2001). Early and meaningful community 
involvement. U.S. Environmental Protection Agency, Office 
of Solid Waste and Emergency Response. Washington, DC. 
OSWER Directive No. 9230.0-99, October 12. Available: 
http://www.epa.gov/superfund/policv/pdfs/early.pdf 

[accessed 12 June 2007]. 

NACCHO (National Association of County and City Health 
Officials). Turning Point: Collaborating for a New Century’ 
in Public Health , see 

http://www.naccho.org/topics/infrastructure/TumingPoint.cf 

m [Specifically, Fourteen Policy Principles for Advancing 
Collaborative Activity Among and Between Tribal 
Communities and Surrounding Jurisdictions. 
http://archive.naccho.org/documents/TP-policv- 

principles.pdf 1. 

U.S. CDC (Centers for Disease Control and Prevention). 
Preventing Chronic Disease [online serial] Available: 
http://www.cdc.gov/pcd/ . 

U.S. EPA (U.S. Environmental Protection Agency) (2005). 
Superfund Community Involvement Handbook. 

[Specifically, chapters 1 through 3.] EPA 540-K-05-003, 
Available: 

http://www.epa.gov/superfund/communitY/cag/pdfs/ci hand 

book.pdf 

U.S. EPA (U.S. Environmental Protection Agency) (1999). 
Risk Assessment Guidance for Superfund: Volume I - 
Human Health Evaluation Manual. Supplement to Part A. 
Community Involvement in Superfund Risk Assessments. 
EPA/540/R-98/042, OSWER 9285.7-01E-P, PB99-963303. 

U.S. EPA (U.S. Environmental Protection Agency) (2000). El 
Superfund Hoy Dia: La Estimacion de Riesgos: Como 
Lograr la Participacion de La Communidad. U.S. 
Environmental Protection Agency, Office of Solid Waste 
and Emergency Response. Washington, DC. EPA 540-K- 
99-005, OWSER 9200.2-26K, PB99-963230. Available: 
http://www.epa.gov/superfund/community/today/pdfs/risk- 

fs-0203.pdf 

U.S. EPA (U.S. Environmental Protection Agency) (2001). 
Improved Science-Based Environmental Stakeholder 
Processes: A Commentary by the EPA Science Advisory 


Board. EPA-SAB-EC-COM-01-006. EPA Science Advisory 
Board. Washington, DC. Available: 

http://vosemite.epa.gov/sab/sabproduct.nsf/CEE3F362F 1A1 

344E8525718E004EA078/SFile/eecm01006 report appna- 

e.pdf 

U.S. EPA (U.S. Environmental Protection Agency) (2003). 
Framework for Cumulative Risk Assessment. Washington, 
DC: United States Environmental Protection Agency. 
EPA/600/P-02/001F. Available: 

http://cfpub2.epa.gov/ncea/cffn/recordisplay.cfm?deid=54944 . 

U.S. EPA (U.S. Environmental Protection Agency) (2003). 
Framework for Assessing Risks of Environmental Exposure 
to Children. Washington, DC. Available: 
http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=22521 . 

U.S. EPA (U.S. Environmental Protection Agency) (2005). 
Guidance on Selecting Age Groups for Monitoring and 
Assessing Childhood Exposures to Environmental 
Contaminants. Risk Assessment Forum, Washington, D.C. 
EPA/630/P-03/003F. Available: 

hltp://cfpub.epa.gov/ncea/cfin/recordisplay.cfrn?deid= 146583 . 

U.S. EPA (U.S. Environmental Protection Agency) (2006). 
Considerations for Developing Alternative Health Risk 
Assessment Approaches for Addressing Multiple 
Chemicals, Exposures, and Effects. External Review Draft. 
71 FR 16306. 

U.S. EPA (U.S. Environmental Protection Agency) (2006). 
Paper on Tribal Issues Related to Tribal Traditional 
Lifeways, Risk Assessment, and Health and Well Being: 
Documenting What We've Heard. The National EPA-Tribal 
Science Council. Available: 
http://epa.gov/osp/tribes/tribal/Triballssues.pdf . 

U.S. EPA (U.S. Environmental Protection Agency) (2006). 
EPA’s Public Involvement Policy. Available: 
http://www.epa.gov/publicinvolvement/policv2003/index.htm . 

U.S. Food and Drug Administration (FDA). Exception from 
informed consent requirements for emergency research. 21 
CFR § 50.24 

University of Kansas Community Tool Box. Available: 
http://ctb.ku.edu/en/tablecontents/ . 

University of Washington Community-Campus Partners for 
Health, Available: 

http://depts.washington.edu/ccph/index.html . 

Veazie MA, Teufel-Shone NI, Silverman G, Connolly A, 
Wame S, King B, et al. (2001). Building community 
capacity in public health: The role of action-oriented 
partnerships. J Public Health Manag Pract 7(2):21 -32. 


78 






















U.S. EPA, Office of Environmental Justice 
Resources: 

Executive Office of the President. (1997). Environmental 
Justice: Guidance under the National Environmental Policy 
Act. Council on Environmental Quality, pp. 7-17). 

Available: 

http://epa.gov/compliance/resources/policies/ei/ei guidance 

nepa ceql297.pdf 

NEJAC (National Environmental Justice Advisory Council) 
(2006). Future mechanisms to enhance stakeholder 
involvement and engagement to address environmental 
justice: A letter report. Available: 

http://epa.gov/compliance/resources/publications/ei/neiac/st 

akeholder-involv-9-27-06.pdf 

NEJAC (National Environmental Justice Advisory Council) 
(2004). Environmental justices and federal facilities: 
Recommendations for improving stakeholder relations 
between federal facilities and environmental justice 
communities. Waste and Facility Siting Subcommittee, 
Federal Facilities Working Group. Available: 
http://www.epa.gOv/compliance/resources/publications/ei/n 

eiac/ffwg-final-rpt-102504.pdf 

NEJAC (National Environmental Justice Advisory Council) 
(2004). Meaningful involvement and fair treatment by tribal 
environmental regulatory programs. Indigenous Peoples 
Subcommittee. Available: 

http://epa.gov/compliance/resources/publications/ei/neiac/ip 

s-fmal-report.pdf 

NEJAC (National Environmental Justice Advisory Council) 
(2000). Guide on consultation and collaboration with Indian 
tribal governments and the public participation of 
indigenous groups and tribal members in environmental 
decision making. Indigenous Peoples Subcommittee. 
Available: 

http://www.lm.doe.gov/env iustice/pdf/ips consultation gu 
ide.pdf 


NEJAC (National Environmental Justice Advisory Council) 
(2000). NEJAC May 200 Meeting Report. Environmental 
Justice and Community-Based Health Model Discussion. 
Available: 

http://epa.gov/compliance/resources/publications/ei/neiac/co 

mmunitv-based-health-recom-report.pdf 

NEJAC (National Environmental Justice Advisory Council) 
(2000). The model plan for public participation. The Public 
Participation and Accountability Subcommittee. EPA- 
300/K-00-001. Available: 

http://epa.gOv/compliance/resources/publications/ei/neiac/m 

odel-public-part-plan.pdf 

U.S. EPA (U.S. Environmental Protection Agency). (2008). 
The Environmental Justice Strategic Enforcement 
Assessment Tool (EJSEAT). Available: 
http://www.epa.gov/compliance/resources/policies/ei/ei- 

seat.html 

U.S. EPA (U.S. Environmental Protection Agency). (2006). 
Environmental Justice Collaborative Problem-Solving 
Cooperative Agreement Program FACT SHEET. Office of 
Environmental Justice. Available: 

http://www.epa.gov/compliance/resources/publications/ei/fa 

ctsheets/fact-sheet-ej-cps-grants-6-13-06.pdf 

U.S. EPA (U.S. Environmental Protection Agency). (2004). 
Toolkit for assessing potential allegations of environmental 
justice. (Section 3.3). Office of Environmental Justice. 
EPA-300/R-04-002. Available: 
http://epa.gov/compliance/resources/policies/ej/ei- 

toolkit.pdf 

U.S. EPA (U.S. Environmental Protection Agency). (1995). 
The EPA’s Environmental Justice Strategy. Available: 
http://epa.gov/compliance/resources/policies/ei/ei strategy_ 

1995.pdf 


79 


































SECTION 7 


Designing and Implementing Strategies for 
Effective Communication 


Successful implementation of observational human 
exposure studies requires effective communications 
between the researchers, study participants, community 
representatives, community members, stakeholders, and 
the public. The previous two sections established the 
need for communications that are “on-going, interactive 
dialogue...involving the disclosure and exchange of 
relevant information, discussion of that information, and 
assessment of the individual’s understanding of the 
discussion” (Recommendation 4.1, IOM, 2002). NIH 
advocates “plain language” that explains the research “in 
an honest, straightforward way” (Recommendation 11, 
NIH, 2005). Indeed, strong relationships can be built 
with participants, the community, and stakeholders only 
if there are clear and effective communications between 
the researchers and the community. The previous section 
illustrates, also, that effective communication is 
bidirectional; it involves listening as well as “speaking.” 
The ethical value of respect for persons, including 
respect for one another’s autonomy and welfare, 
demands that researchers, participants, community 
members, and stakeholders strive to establish effective 
communications and to foster a relationship of trust and 
respect. The researchers should make a commitment to 
effective communications and make the appropriate 
investment of time and resources to ensure that the 
communications are at an appropriate level and are truly 
effective. Researchers should regard communications as 
intrinsic to the ethical basis for the study. 

With the ethical basis for bidirectional 
communication assumed as a given, and the need for 
open and honest bidirectional communications having 
been well established in the previous sections that 
discussed relationships between the researchers and the 
participant (Section 5) and the researchers and the 
community (Section 6), this section discusses strategies 
and tools that researchers may find useful in developing 


effective communications. The focus in this section is 
primarily from the perspective of “getting the word out,” 
because that is the aspect of communication most under 
the control of the researchers. Nonetheless, effective 
communications will be bidirectional and involve 
effective listening. Researchers should keep in mind that 
it is as important to listen to the participants, community, 
and other stakeholders as it is for the researchers to 
provide them with information using the approaches 
described in this section. 

7.1 Communication Strategy and 
Implementation Plan 

Fundamental to achieving effective communications 
are a communications strategy and implementation plan. 
In general, the goal of the communication strategy and 
plan is to clearly define how effective bidirectional 
communications will be achieved in the study. Specific 
goals should be developed based on the specifics of the 
study design, the study population, the community, and 
the stakeholders. The plan will describe who will be 
involved in the communications, what communications 
are required, and how the communications will be 
performed. The communication strategy and 
implementation plan should be developed early in the 
planning stages of a study. The communication plan, 
however, needs to be dynamic, with revisions and 
updates occurring throughout, the study and in 
collaboration with the community and stakeholders. 

Text Box 7-1 lists elements that should be included 
in a communication plan. The communication strategy 
should be developed based on the goals of the study and 
an understanding of the background, education, 
attitudes, and opinions of the stakeholders and the 
community that will be involved in the many different 
aspects of the study from the initial conceptualization to 
the final reporting of the study results. 


81 



Text Box 7-1. Elements in a Communication Plan 

• Background information description (overview) of the study, 
relevant historical background information, statement of 
communication needs, and identification of communication 
opportunities and issues 

• Purpose and goals of the communication strategy 

• List of individuals and groups involved in the communications, 
plus relevant demographics and other information to profile the 
groups 

• Strategy and approach for achieving the goals, including a 
statement of the primary message to be conveyed and 
descriptions of the communication channels 

• Activities and materials to achieve the goals of specific 
elements of the plan to be performed 

• Timetable 

• Roles and responsibilities 

• Resources needed (budget) 

• Measures of effectiveness 


Careful planning is required to develop a 
communication plan that will be effective. The research 
team has to invest the time and resources necessary to 
develop and implement the plan. They also should 
recognize that the communication plan is essential for 
conducting the study and is just as important as the study 
design, human subjects research protocol, or QAPP. The 
observational study, if properly justified as described 
earlier, provides a social and scientific value and brings 
benefit to society (and perhaps the participants); it 
should be a program that the researchers want to discuss 
and explore with the public. The communication plan 
and strategy provide the researchers with an opportunity 
to create effective bidirectional communications with the 
participants, community, and stakeholders. They are not 
simply a way to “avoid problems” with the community, 
stakeholders or the media nor only a plan for reacting to 
“negative” feedback. 

Recognizing that the communication strategy must 
address the bidirectional nature of communications with 
the study participants and the community to be effective, 
it is important that the communication strategy and 
implementation plan be developed in collaboration with 
the community and other stakeholders. As discussed in 
previous sections, members of the community in which 
the study will be performed will provide valuable input 
into the development of the communication strategy by 
providing information about the community culture, 
norms, attitudes, perceptions, etc. They will provide, not 
only expertise about the community, but also 
experiences and lessons learned about previous 
communications activities in the community. It is 
important to engage community representatives and 
stakeholders early in the process of development of the 


communication strategy, the implementation plan, and 
the communication tools. 

Researchers also may find it helpful to seek 
guidance on how to communicate more effectively, 
especially because that is not a routine part of their 
training or experience. They may consult and learn from 
communications specialists in their organization. In 
addition, a wide variety of resources are available. For 
example, the Federal Communicators Network (FCN) 
( www.fcn.gov ) has prepared a “communicators guide” 
that offers advice on how to communicate—in plain 
language, in easily digestible “chunks,” and in a form 
that will be used. They emphasize that “good 
communication is difficult because it requires a lot of 
effort, time, and patience” (FCN, 2001). Some tips from 
the guide to help federal communicators get their point 
across are listed in Text Box 7-2. 


Text Box 7-2. Tips for Getting Your Point Across 

• Be prepared. 

• Be confident. 

• Stay focused on your conversation and your listener. 

• Maintain eye contact with your listeners. 

• Make sure your listeners are following you by asking them for 
questions or feedback. 

• Do not lose your temper or get over-emotional. 

• Speak slowly and calmly; don’t raise your voice. 

• Speak clearly and concisely. 

• Get to the point; do not ramble. 

• Be kind, compassionate, and empathetic. 

• Be honest; do not play games. 

• Be assertive but tactful 


7.2 Individuals and Groups Involved in the 
Communications 

An effective communication plan will identify and 
involve all of the individuals and relevant groups that 
should be included in the communications efforts. When 
conducting observational human exposure studies, this 
list may be quite long. Although researchers may desire 
to limit the number of individuals and groups involved 
to keep the effort as simple and focused as possible, they 
need to ensure that all potential stakeholders are 
identified. The communication plan should identify all 
groups, including community organizations and 
stakeholders, involved in a study, their roles and 
responsibilities in the study, how communications will 
be developed with each group, and the timing of the 
communications. It is likely that most studies will 
involve the individuals, community groups and 
stakeholders shown in Text Box 7-3. 


82 















Text Box 7-3. Individuals and Groups 
Involved in Communications 

• Principal investigator—the researcher with ultimate 
responsibility for the study 

• Research team 

• Study participants 

• Third parties associated with study participants (e.g., spouse, 
children, landlords) 

• Community representatives 

• Community members 

• Governments (local, State, and Federal) 

• Study institution management 

• Study sponsors or funding organization 

• Organizations with interest in the participants, the community, 
or the research question 

• Stakeholders that may be impacted by the results of the study 

• The scientific community 

• Media 

• The general public 

The study participants are a key group involved in 
communications during a study and are easily identified. 
Similarly, it is generally not difficult to identify the third 
parties associated with the study participants, because 
these groups must be identified when considering ethical 
issues in the study and when developing the human 
subjects research protocol. Research teams should ensure 
that the communication strategy includes the strategy 
and approach for third-party communications. 

As discussed in Section 6, it is critical that 
community representatives are identified early in the 
scoping and planning phase of the study. It is important 
that researchers are informed about the community in 
which they will conduct the study and understand the 
unique characteristics and culture of the community and 
the potential study participants to develop effective 
bidirectional communications. When possible, 
researchers should identify other research organizations 
who have worked in the community and attempt to 
gather information from them on the nature of the 
community, who represents the community, and what 
communication strategies have been used previously in 
the community. Understanding how the community 
defines itself or thinks of itself is critical to establishing 
effective communications. 

Identification of all relevant stakeholder groups may 
be more difficult. As defined in Section 6, the term 
stakeholder is used here to identify a person or group 
who has a valid interest in an activity or decision, but 
who does not speak directly for the community or the 
participants. There may be many organizations who 
consider themselves as stakeholders that represent the 


interests of the community, the participants, or the 
research problem. For example, there are many nonprofit 
organizations that advocate for the protection of 
children’s health. When conducting an observational 
study involving children, the research team should 
identify those groups that could have an interest in the 
study. They need to be identified in the communication 
plan, and an approach needs to be developed for 
communicating with them about the study. There are 
many sources of information on potentially interested 
stakeholder groups. This information can be obtained 
from the research team based on similar studies, the 
participants, the community representatives, sponsoring 
organizations, and “umbrella” organizations for various 
advocacy groups. The Internet has made identification of 
the various stakeholder groups easier and is a source of 
information on goals of the groups and contact 
information. Approaches for communications with these 
and other groups on the list are discussed further in the 
following subsections. 

Researchers should recognize that identifying and 
involving all pertinent community and stakeholder 
groups in their observational human exposure studies is 
important for effective communications and the potential 
success of the study, but that there is the potential for the 
group to become so large that it becomes difficult to 
manage. Large groups not only have the potential for 
impeding progress on a research effort simply because of 
the logistics of the interactions within the group, but, 
also, because of the potential for conflict between the 
groups. It is essential, therefore, that researchers attempt 
to maintain stakeholder groups of manageable size and 
be prepared to deal with potential conflict within the 
groups. There is extensive literature available on conflict 
management, but it is outside of the scope of this 
document to recommend specific approaches or 
literature references. 

7.3 Communications Timetables—When 
To Communicate 

Communications begin with the initial 
conceptualization of the study and continue through the 
reporting of the study results and beyond. Even after a 
study has ended, followup communications may 
continue with the study participants, the community, the 
scientific community, and the public. It is beyond the 
scope of this document to lay out timetables for 
communications in observational human exposure 
studies because timing will differ with each study. The 
following discussion highlights a few of the issues 
associated with the timing of communications to ensure 


83 




that they are effective. This section also does not discuss 
communications among the research team, research 
organization, or study sponsors. 

Researchers should begin the dialogue with the 
community as soon as possible during study 
conceptualization and planning. Once the community in 
which the study will be performed is identified, 
community representatives should be identified and 
contacted to discuss the potential study and to get input 
on how the study may be designed. As discussed in 
Section 6, the observational human exposure studies 
discussed in this document are generally not CBPR. 
Although the study objectives or hypotheses have been 
defined and the general approach has been developed, 
the community still can provide valuable input about 
their environmental or public health concerns. Again, as 
discussed earlier, the planning for the study should be 
flexible enough to incorporate community concerns 
where feasible. Recognizing that many observational 
human exposure studies will not be able to address all of 
the community’s concerns, it is important that the 
communications with the community accurately convey 
the value, merit, and benefits from the study that will be 
relevant to the community. 

Press releases can serve as useful tools for informing 
communities about upcoming studies and for identifying 
stakeholders. Assuming that community representatives 
have been identified early in the development of the 
study design and communications strategy, and that 
community buy-in for the study has been gained, 
researchers can work with community leaders and 
community members to develop press releases and other 
communication tools. Press releases can serve multiple 
purposes. They provide information to potential 
community representatives who may not have been 
identified by the researchers as potential collaborators in 
the study. They provide publicity that will inform 
community members about potential contacts by the 
research team (e.g., in a random sample design). They 
provide information to public interest and advocacy 
groups who may feel that they are stakeholders who 
should be involved in the study. Press releases also 
provide the transparency for the study and the research 
team that is essential for building trust. 

Studies also should be announced to stakeholders 
and the public (via the media, community interactions, 
or other means) well in advance of study 
implementation. Large grants expected to have 
significant impact in communities often are announced 
by EPA at the research institution receiving the grant 
and in press releases to the local media. These studies, 


therefore, are publicized at a very early stage. 
Cooperative agreements, which are another mechanism 
by which the government funds some research projects, 
are announced in the same way. Cooperative agreements 
and studies performed by EPA researchers receive 
additional public notice when they are reviewed by the 
Office of Management and Budget (OMB) under the 
Paperwork Reduction Act. All studies involving 
collection of survey information from more than nine 
people are reviewed by OMB. This involves submission 
of an Information Collection Request (ICR) to OMB, 
announcement of the ICR in the Federal Register , and 
an opportunity for public comment. A docket is 
established specifically to facilitate public comment. 
This process results in widespread publication of 
upcoming government research studies through scrutiny 
by concerned stakeholder groups who routinely review 
the announcements in the Federal Register. 

Prior to the start of data collection in a community, 
relatively large-scale communications may be required. 
These communications may involve notifications to 
public safety officials about the presence of the research 
team in the community, press releases to local media 
outlets about the study, and meetings with community 
groups to provide details about data collection activities. 

It is essential that the research team fosters 
continuing bidirectional communications with the 
participants, community, and stakeholder groups 
throughout the study to maintain transparency, trust, and 
interest in the study. This can be aided by providing 
project progress reports and interim results to the 
participants and the community through community 
meetings, mailings, or Web sites. In observational 
human exposure studies with repeated measurements 
over seasons or years, routinely meeting with 
participants can serve as a mechanism for providing 
study information to the participants and receiving 
feedback from the participants and the community about 
the study and their roles in it. Effective bidirectional 
communication with participants can be expected to 
improve their participation in the study (e.g., in 
completing surveys and collecting personal samples) and 
for improving retention in longitudinal studies. 
However, it is essential that the researcher recognize the 
implications of such meetings on privacy and 
confidentiality issues for the participants and develop 
communications to advise the participants of these 
issues. 

Community meetings also are effective for 
maintaining communications throughout a study. They 
provide the opportunity to disseminate information to 


84 


community representatives and to obtain feedback. They 
also provide an opportune setting for news releases to 
the media to maintain or increase interest in the study. 

7.4 Communicating at Different Levels 

The diversity of interested people and groups often 
means that communications materials should be 
developed at different levels of scientific literacy. In any 
case, the materials should all be written in “plain 
language” that is honest and straightforward. Stableford 
and Mettger (2007) state that “plain language embodies 
clear communication.” Many researchers mistakenly 
believe that the term means just using simple words, or 
worse, “dumbing things down.” It actually refers to 
communications that engage and are accessible to the 
intended audience. 

A 1998 Presidential memorandum required that 
“plain language” be used in all governmental 
communications with the public. That memorandum 
stated, “By using plain language, we send a clear 
message about what the Government is doing, what it 
requires and what services it offers. Plain language saves 
the Government and the private sector time, effort, and 
money.” Plain language is reader friendly and designed 
to increase the participant’s understanding of the 
communication material. It serves as a means by which 
lay audiences can access and understand scientific 
information. Researchers desiring to use plain language 
in their verbal and written communications with 
communities must decide on key messages to include 
and delete unnecessary descriptive, bureaucratic, or 
jargon-filled language. Researchers should use words 
that commonly are understood, rather than difficult 
abstract terms and concepts. A friendly, conversational 
tone is used to engage the lay audience, rather than a 
formal, scholarly tone that distances the community. 
Stableford and Mettger (2007) argue that proficiency in 
creating appropriate plain language materials is an 
acquired skill that requires knowledge and experience. 
“It is both an art and a science, requiring the ability to 
simultaneously think about the cognitive, emotional, and 
visual appeal of the piece as well as applying research- 
based strategies to ensure a truly easy-to-read and 
understand print material.” 

The Department of Health and Human Services 
(HHS) has developed a Web site that specifically 
address the issues related to “plain language” (see 
http:/Avww.health.gov/communication/literacy/plainlang 
uage/PlainLanguage.htm ). The site includes a list of 
references and other helpful resources. 


To maintain community engagement through the 
research process, it is critical that communications are at 
the appropriate level, and that materials are written at a 
reading level that is appropriate to the audience. For the 
nonscientist, many IRBs and other groups target 
materials to be used with participants and communities 
at a reading level no higher than the 8th grade to improve 
the likelihood of comprehension. In some communities, 
however, other factors, like primary languages other than 
English, educational disadvantages, etc., may require 
communications materials to be written in alternate 
languages and at different reading levels. The issue is 
comprehension, as was discussed in Section 5.1.2. 
Empirical testing of communication methods and 
content is essential to ensure comprehension (Health 
Canada, 2006). 

Researchers also should recognize that in this 
information age, dissemination of informational 
materials may be rapid and widespread. Therefore, even 
documents intended for scientific peers may benefit by 
including summary information in an executive 
summary or preface that a lay reader can understand. 

7.5 Communications Materials 

Researchers need to communicate clearly with the 
many groups listed in Section 7.2 to develop their 
relationship with the participants in the study, to develop 
their partnership with the community, to gain support 
from stakeholders, and to inform the public. To achieve 
the multiple purposes of communications during a 
research study and to communicate with many diverse 
groups, a variety of communications materials may need 
to be developed. Different materials have different 
purposes and different types of information to be 
communicated. Because of diversity in interested 
individuals and groups with respect to education, 
cultures, information needs, etc., the format and content 
of communication materials likely will need to be 
diverse. Text Box 7-4 list activities and materials that 
may be helpful in facilitating communications. 

By definition, communication is an exchange of 
information. This has to be the primary goal of 
communication activities. The accuracy and 
completeness of the information transferred is important. 
There are many different ways to communicate, the 
effectiveness of which varies substantially. The way in 
which the information is conveyed is as important as the 
information itself. Effective communication should 
promote trust and credibility. Peters et al. (1997) found 
that three determinants, namely, (1) knowledge and 
expertise, (2) openness and honesty, and (3) concern and 


85 





care, were important factors determining perceptions of 
trust and credibility. Therefore, the approach to 
communication in observational human exposure studies 
should consider these factors, and communication 
materials should be developed with these factors in 
mind. 


Text Box 7-4. Activities and Materials That 
May Be Useful in a Communication Plan 

• Flyers 

• Web sites 

• Brochures 

• Interviews 

• Newsletters 

• Focus groups 

• Presentations 

• Direct mailings 

• Press releases 

• Questions and answers 

• Desk statements (government) 

• Abstracts 

• Study reports 

• Talking points 

• Community meetings 

• Stakeholder meetings 

• Technical presentations 

• Study participant meetings 

• Scientific meeting presentations 

• Peer-reviewed scientific journal manuscripts 

• Final reports describing the total research effort 


When developing communication materials, the 
researcher should consider the needs of the reader, 
listener, or viewer with respect to content, scope, style, 
and the level at which the materials are written. There 
are many sources of information on design of 
informational materials, such as flyers or brochures. For 
example, Alderson (1995) provides an example of the 
recommended content and style for information leaflets 
(that also may be flyers or brochures) for pediatric 
medical research. She suggests that leaflets be provided 
to parents of children who will be study participants that 
can be read to the children. She recommends that these 
be provided at the time that the parent is being informed 
of the study, prior to requesting the informed consent. 
The content of the leaflet would include the following 
topics. 

• Nature and purpose of the research 

• Anticipated benefits of the research 

• Risks, harms, costs, and inconvenience to the 
participant 

• Assurance that the participant freely can refuse to 
participate in or withdraw from the study 


• Details about remuneration 

• Names of the project sponsors and the researchers 

• Contact information for the researchers 

• Respect for privacy and confidentiality 

Leaflets and brochures that contain this information 
provide a tool for communication with study 
participants. However, these materials need to be written 
carefully using everyday terms that the average 
nonresearcher can understand. The brochure should be 
written in a friendly style that conveys the intent of the 
researcher to engage the reader as a collaborator on the 
study, not as a study “subject,” who will be told to do a 
series of tasks while participating in the study. 

These same leaflets and brochures can be used to 
inform other groups that either may be involved or 
interested in the study, such as community 
representatives, stakeholder organizations, the media, 
and the general public. The researcher should ensure that 
any brochure developed for the study includes accurate 
and complete information that is less likely to be 
misinterpreted by anyone who might pick up the 
brochure. Brochures and flyers that are used to announce 
a study or are used as recruiting tools should be carefully 
written in plain language to ensure that there is not a 
perception of activities that are unethical. For example, 
if flyers announcing a study state that study participants 
will be compensated, the flyer needs to ensure that the 
compensation is not the focus of the flyer, and that the 
payment does not appear to be excessive and coercive 
(see Section 5.2). Flyers announcing a study generally 
do not include the dollar amounts of payment. 

Researchers need to have similar concerns about all 
of the communication materials that are developed, 
regardless of the type of material, whether it is a direct 
mailing, a Web site, a news release, or a set of questions 
and answers (Q&As) used to respond to media or 
stakeholder inquiries. In developing the communication 
materials, the research staff should seek the assistance, 
advice, and input of people in their organization and 
community groups with experience in developing such 
materials. With all of these materials, the researchers 
should be concerned with how the materials could be 
misinterpreted, and whether there could be a perception 
that the study would not meet the highest scientific and 
ethical standards. In this age of rapid communications 
and increased accessibility to information, it is essential 
that communication materials are well developed, 
accurate, and understandable to all audiences that may 
read them. 

Research study Web sites are especially useful for 
communicating information about observational human 


86 




exposure studies. Web sites should be developed early in 
the study to disseminate information to stakeholders and 
the community. Additionally, the sites can be set up with 
participant-only pages to provide more detailed 
information to study participants, including information 
on study protocols that require participant assistance 
(e.g., protocols for collecting urine samples, 
time/activity log entries). However, researchers need to 
ensure that Internet access is available to their intended 
audience and be prepared to provide alternative 
communication tools for those without such access. 

The plan for disseminating information from the 
study should be developed in the early design phases of 
the study and should be included in the study design 
document. Sufficient resources, both time and funding, 
need to be budgeted for this activity. 

7.6 Informing the Study Participants and 
Communities 

Effective communications require that all parties, 
researchers and participants alike, involved in the 
communication understand the content and context of 
the information being exchanged. “When researchers 
discuss a planned study with community representatives, 
understand their concerns and needs, and respond to 
them, protocols can be strengthened both scientifically 
and ethically” (p. xii, NRC & IOM, 2005). 
Comprehension is one of the key pillars of informed 
consent, and it means that participants understand the 
key elements of the research. The most effective way to 
improve comprehension is by talking one-on-one with 
study participants. 

To accomplish that, the researchers need to make a 
commitment to communicating with both the study 
participants and the community to inform them of the 
study and provide training as appropriate. This can 
require a substantial investment of time and resources, 
but it is critical to the success of the study. 

Working with study participants to inform them 
about the study and the scientific basis of the study will 
have many benefits. The more educated the participant is 
about the purpose of the study and the activities to be 
performed during the study, the more likely the 
participant will be to develop a beneficial researcher- 
participant relationship. By taking the time to inform the 
participant, the researcher demonstrates his or her 
commitment to the participant and conveys the 
importance or value of their participation in the study. If 
the researcher-participant relationship is well developed, 
the participant will have a higher level of trust in the 
researcher and will be likely to have more interest in the 


study and a positive outcome. If such a relationship is 
developed and the participant is informed about the 
study goals, the participant will take part more readily 
and effectively in the specific study activities. For 
example, a study participant who understands why 
time/activity information is critical to understanding 
exposure is likely to do a better job completing a 
time/activity log than a participant with no interest in the 
outcome of the study. In addition, an informed 
participant may have good suggestions for improving the 
study and the interactions with the participants and the 
community that the researchers should listen to and 
adopt. Developing the researcher-participant relationship 
and informing the participants also should improve 
retention in longitudinal, repeated measures studies 
because the participant feels that he or she is 
collaborating with the researcher and is not merely a 
study “subject.” 

Similarly, providing information on the research 
study to the community should provide significant 
benefits in terms of support to the research team and 
working with the team to facilitate the study in their 
community to address both the scientific issues and the 
community’s concerns. If community leaders understand 
the research problem, the study goals, and the study 
activities, they can more effectively articulate the 
community’s concerns to the researchers and integrate 
those issues into the study design. This will enhance 
their work with the research team during the design 
phase and will enable them to more effectively advise 
and assist during the implementation of the study. 

7.7 Reporting Study Results to the 
Participant and Community 

Researchers need to develop the approach for 
reporting results to the participants, community, 
stakeholders, media, and others during the initial 
planning of the study. There are not well-developed 
guidelines for when and how to report study results 
(Parkin, 2004). In her systematic review of guidelines 
and frameworks for reporting study results, Parkin 
determined that locating guidance may be difficult and 
time consuming for researchers. She found agreement on 
the importance of disseminating study results to produce 
public health benefits, but there is not a consensus on 
when and how results should be reported to either 
communities or study participants. Although she did not 
identify well-developed guidance documents, she did 
identify some common themes. The first was that 
researchers are becoming aware of the importance of 
systematic planning of the research communications, 


87 


planning that needs to be done early in the study. 
Second, organizations are recognizing the importance of 
communicating with communities. And, third, research 
professions are recognizing the importance of research 
communication and their responsibilities. 

There is a large body of literature on processes for 
risk communication (e.g., see Covello et al., 1989, 2007; 
U.S. HHS, 2002; ASTDR, 2007). Processes for risk 
communication are highly relevant to reporting results 
from observational human exposure studies, even though 
they may not include measurements of health outcomes 
or risk assessments. 

HHS has prepared a useful document entitled 
Communication in a Crisis: Risk Communication 
Guidelines for Public Officials, 2002. It is available 
online and in hard copy and includes a chapter on 
communicating complex, scientific, and technical 
information (U.S. HHS, 2002). They recommend using 
clear, nontechnical language, avoiding jargon, and 
putting technical terms into frames of reference that the 
public or other listeners can understand. 

Covello and Allen (1988) described seven cardinal 
rules for risk communication (Text Box 7-5) that are still 
quite applicable today. More recently, Covello et al. 
(2007) have developed a “message mapping” approach 
for risk communication. Message mapping is a process 
to anticipate the questions likely to be asked after an 
incident and to prepare, clear and concise answers to the 
anticipated questions in advance. The approach builds on 
an understanding of current communications practices 
(e.g., short messages averaging 27 words, soundbites of 
around 9 seconds, the most frequently asked questions 
after an incident) and typical human responses to crisis. 
The report lays out a series of steps to develop short, 
clear key messages to address stakeholder concerns in 
advance. 


Text Box 7-5. Seven Cardinal Rules of 
Risk Communication 

(Covello and Allen, 1988) 

1. Accept and involve the public as a partner. 

2. Plan carefully and evaluate your efforts. 

3. Listen to the public’s specific concerns. 

4. Be honest, frank, and open. 

5. Work with other credible sources. 

6. Meet the needs of the media. 

7. Speak clearly and with compassion. 


The report also provides useful approaches for 
effectively communicating the messages in times of 
crisis. It emphasizes that during a crisis, “people judge 


the messenger before the message and they base their 
judgment in terms of trust.” In times of crises, opinions 
about trustworthiness hinge largely on perceptions of 
caring and empathy, whereas competence and expertise 
are key factors when there is little or no stress. Figure 7- 
1 is taken from the Covello et al. (2007) report and 
represents the relative importance of various factors in 
influencing whether or not people trust a speaker in 
times of crisis. Many of the principles and processes for 
crisis communications are applicable for communication 
of research results from observational human exposure 
studies, and the reader should consult the risk 
communication literature. 


Listening/Caring/Empathy 

50 % 


Honesty/ Dedication/ 

Openess Commitment 

15 - 20 % 15 - 20 % 

Competence/ 

Expertise 
15 - 20 % 



Figure 7-1. Factors Influencing Trust in Times of Crisis 

EPA. 2007 


ATSDR (2007) has A Primer on Health Risk 
Communication Principles and Practices available 
online. Because ATSDR generally responds to 
environmental issues identified by individuals or 
communities, their guidance focuses on communicating 
with individuals and communities that perceive an 
imminent or significant health risk because of a problem 
in the community. Because ATSDR often enters a 
community after a potential problem has been identified, 
ATSDR communications are often reactive, by 
necessity, rather than proactive. 

Health Canada (2006) has recently published The 
Strategic Risk Communications Framework. The focus 
of the effort is always the stakeholders. Health Canada’s 


88 





process aims to involve the interested and affected 
parties at all points in a “dialogue-based” 
communication process. (See Text Box 7-6). 


Text Box 7-6. Steps in Health Canada’s Risk 
Communication Framework 

1. Identify the issue and its context—define the opportunity and 
characterize the situation. 

2. Assess the risks and benefits—assess stakeholder perception 
of the risks, benefits, and tradeoffs. 

3. Identify and analyze options—assess how stakeholders 
perceive the options. 

4. Select a strategy—develop and pretest strategies, risk 
communications plans, and messages. 

5. Implement the strategy—implement risk communications. 

6. Monitor and evaluate results—evaluate risk communications 
effectiveness. 


Guidance on risk communication strategies and 
practices consistently stresses the importance of 
obtaining input and feedback from community 
representatives, who can assist in developing approaches 
that place the results in relevant contexts for the 
community and the participant. 

One of the difficulties in reporting results to 
participants and communities is timely reporting because 
it generally takes a long time to complete both the 
chemical and data analyses in large studies. Researchers 
desire to report fully validated and analyzed data to 
study participants and to the community. But, delay in 
reporting data can create a number of difficulties. 
Participants may move before they receive results. They 
also may lose interest in the study, or more importantly, 
lose trust in the researchers and the scientific research 
community if they do not receive their results in a timely 
manner. Similar problems may occur in the community 
as community leaders and representatives change. 
Community representatives may have expectations for 
data and information that researchers cannot achieve. 
Therefore, it is important that researchers clearly 
communicate with the participants and the community 
about what results will be provided and when they will 
be delivered so that expectations do not differ from 
“reality.” 

Reporting study results from observational human 
exposure studies can be particularly challenging because 
data on exposure concentrations and the factors 
impacting exposure may be difficult to relate to a health 
outcome that is relevant to the study participant. Health 
effects data is often lacking for the concentrations at 
which chemicals or their metabolites are measured in 
environmental or biological media. This is especially 


true for studies of many chemicals for which acceptable 
occupational exposure levels have been established, but 
for which there are not environmentally relevant 
standards for low-level exposures. Williams (2004) 
describes an approach for communication using 
comparative risk analyses. She describes intrachemical 
comparisons, interchemical comparisons, comparisons to 
background levels of risk, comparisons to theoretical 
risk or safety levels, and risk comparisons to other 
actions or activities. Williams also includes an extensive 
list of references for guidelines and other information on 
risk communication. Readers of this document should 
refer to her manuscript to determine which approach 
may be applicable to their particular study. 

During longitudinal studies with repeated 
measurements over months, seasons, or years, it is 
important that researchers commit to providing interim 
and ongoing results to participants and the community as 
the study proceeds. It is important to maintain the 
researcher-participant relationship throughout the study. 
This can be facilitated by keeping study participants 
informed of the study progress and of the interim results 

Researchers also should recognize that there may be 
potential risks to the study participants, third parties, or 
the community because of results generated from a study 
(refer to Text Box 7-7). Therefore, providing 
information to communities has to be done thoughtfully 
and with appropriate preparation. Processes should be 
developed that provide participants with the option to 
receive, or decline, study results. Researchers should 
work with community groups to determine how study 
results should be disseminated to the community and 
what communications strategies should be used. 


Text Box 7-7. Potential Harms of Sharing Research 
Results with Participants 

(Fernandez, Kodish, and Weijer, 2003) 

• Incorrect or harmful decisions based on uncertain or unreliable 
results 

• Causing distress for those participants who did not benefit 
from the research 

• Rekindling old memories and emotions, especially in the 
setting of serious illness 

• Emotional distress among community members 

• Possible discrimination in obtaining employment or insurance 
for a participant identified by the research to be at high risk of 
developing complications 

• Financial costs to participants and to researchers 


There are a variety of methods for providing study 
results to participants and the community. Fact sheets 
can be used to describe the study and provide general 


89 






study findings to the community and stakeholders. 
Individualized fact sheets can be used to disseminate 
results to the individual participants. Meetings with 
study participants have been used to disseminate study 
information. Community meetings also can be used to 
provide updates on study progress and general results. 

Examples of the processes and the materials used for 
dissemination of information are included in case studies 
described by Israel et al. (2005) and others conducting 
CBPR studies. 

Overall study results generally are disseminated in 
peer-reviewed journal manuscripts and study reports. 
The availability of results published in manuscripts and 
reports has been greatly enhanced by posting them on 
Internet Web sites. For example, all EPA reports are 
now available electronically via EPA’s National Service 
Center for Environmental Publications Web site 
( http://www.epa.tJQv/ncepihom/ ). 

7.8 Reporting Unanticipated Results or 
Observations 

The previous subsection discussed reporting of 
routine results from observational human exposure 
studies. The communication plan should include 
processes and procedures for the dissemination of the 
study results. Additionally, the communication plan 
needs to integrate with the data and safety monitoring 
and oversight plans for the study and include a plan for 
reporting unanticipated results or observations. 
Unanticipated results may include measurements of a 
chemical at a concentration that exceeds what is 
considered to be an “acceptable” level in environmental 
media or biological fluids. Unanticipated observations 
might include observation of the use of a chemical not 
approved for indoor use, storage of chemicals in 
inappropriate containers, storage of chemicals in places 
accessible by children, etc. Unanticipated results or 
observations may be directly related to the research 
question being addressed in the study (e.g., 
measurements of pesticide residues in a home) or 
nonstudy hazards (e.g., frayed electrical cords that may 
pose a hazard to young children and residences). 
Section 4 discusses issues that may affect privacy and 
confidentiality. Section 4.3 covers collateral 

observations of nonstudy-related hazards, including 
those that States may mandate must be reported. 
Section 4.5 discusses the need for data and safety 
monitoring and oversight, including the development of 
plans to report and react to anticipated or unanticipated 
adverse events or conditions. 

As part of the study implementation plan and the 


communication plan, researchers should develop a 
protocol for how to identify contaminant measurements 
and exposures of “concern” that should be reported to 
the study participant as quickly as possible because of 
the potential risk associated with the exposure (see 
Section 4.5, Data and Safety Monitoring and Oversight, 
and also Section 2.7.1, Establishing Criteria and 
Standards for Monitoring Scientific and Ethical Issues 
During a Study.) The plan needs to include the protocol 
for making the determination and the criteria that will be 
used as the threshold or “trigger” for reporting. The 
plans should describe how the results will be reported to 
the participants and what additional action will be 
undertaken to assist the participant in reducing their 
exposures. The first step in developing the protocol is to 
identify what measurement will be used to identify 
exposures of concern. In observational human exposure 
studies, this will generally be the chemical measurement 
in either environmental or biological samples. For 
example, measurement of lead concentration in blood 
would be an appropriate exposure metric if the research 
question being addressed involves lead exposure. The 
measurement is relatively simple and can be performed 
with a short turnaround time. Similarly, measurements 
of chemicals in blood may be appropriate for other 
persistent chemicals that have relatively long half-lives 
in blood. For nonpersistent chemicals, biomarkers of 
exposure measured in urine or saliva may be appropriate 
metrics to identify exposures of concern. For some 
chemicals (e.g., PM, volatile organic compounds 
[VOCs], ozone), biomarkers of exposure either are not 
available or difficult to measure or interpret. In these 
cases, measurements in environmental media may be the 
best exposure metric. Whatever metric is chosen, it is 
important that the chemical analyses can be performed 
relatively quickly to reduce such exposures as quickly as 
possible. 

The second, and more difficult, step in developing 
the reporting protocol is to determine the level of 
concern that triggers reporting of the concentration to the 
study participant. For some environmental media, such 
as drinking water, EPA (2007) has established maximum 
contaminant levels that can be used as triggers for 
reporting. For example, if the researcher measures a 
level of arsenic in drinking water above 0.010 mg/L, he 
or she would be expected to report the level to the study 
participant. For other environmental media, such as air, 
there are few applicable standards. The National 
Ambient Air Quality Standards might be used for the 
criteria pollutants. Guidelines for occupational 
exposures, such as threshold limit values (TLVs) and 


90 



biological exposure indices (BEIs) published by the 
American Conference of Governmental Industrial 
Hygienists (ACGIH, 2008) also may be used. TLVs are 
not standards; ACGIH formulates a conclusion on the 
level of exposure that the typical worker can experience 
without adverse health effects. Many people would 
argue that the TLVs are not conservative enough for the 
average population, particularly not for vulnerable 
lifestages (e.g., children, the elderly) and TLVs are only 
for exposure by inhalation. WHO (2005) also publishes 
air quality guidelines. These types of guidelines can be 
used to advise study participants if their exposures are 
high relative to the guidelines. Reporting levels should 
be conservative, but not so low that reporting the level to 
the participant causes unwarranted concern and stress. 
For other environmental media measured in 
observational human exposure studies, such as house 
dust or surface wipes, the measurement results cannot be 
used easily to estimate exposures, and they are a poor 
metric if used alone. 

An alternative approach to comparison of 
measurement results against available guidelines and 
standards is the comparison of measurements in 
biological fluids to measurement data available from the 
National Health and Nutrition Examination Survey 
(NHANES). For example, results of measurements of 
chemicals or their metabolites in urine or blood can be 
compared to different percentiles (e.g., the 95th) 
reported in the NHANES national reports (CDC, 2005). 
This type of comparison shows that the participant’s 
measurements are at the high end of the distribution of 
the NHANES data, suggesting that action may need to 
be taken to mitigate exposures. However, researchers 
need to be judicious in the selection of the exposure 
metric. Biomarkers in blood and biomarkers in urine can 
be very different exposure metrics and may represent 
different aspects of the exposure event. A similar 
approach could be taken with measurements of 
chemicals in environmental media if there are 
sufficiently large databases available for comparison. 
For many chemicals and many media such databases are 
not available. In some NERL studies, one comparison 
approach that has been used is to compare an 
individual’s environmental media measurements to the 
50th, 75th, or 95th percentile concentrations for the 
entire study population, so that the participant can 
evaluate his or her measurement results relative to those 
of the other study participants. 

A more complex approach than using simple data 
comparisons is to calculate a reporting level defined as a 
chemical or metabolite concentration indicative of an 


absorbed dose greater than that of a target level (for 
example one-tenth) of a lifetime reference dose (RfD) 
level. For a pesticide, the absorbed dose could be 
estimated from the urinary pesticide metabolite level 
using an approach similar to the methodology published 
by Fenske et al. (2000). This deterministic approach to 
dose estimation allows direct back-calculation of doses 
from urinary metabolite concentrations using few 
assumptions and is consistent with current pesticide 
regulatory procedures for risk assessment. When using 
this approach, the research team will need to determine 
how conservative the reporting level should be, as there 
are no guidelines available for using this approach. If the 
concentrations of a metabolite measured in a study 
participants’ urine level are indicative of elevated 
exposures (i.e., above the reporting level), the 
researchers would be expected to report the information 
to the participants and provide information or local 
contacts that could assist in helping the participants 
identify sources of exposure and reduce their exposures. 
Although this would seem to be a reasonable approach 
for some classes of chemicals, the authors are not aware 
of reports of the use of this approach in the scientific 
literature. 

7.9 Anticipating and Responding to 
Criticism 

As discussed in other parts of this document, in spite 
of researchers best intentions, there may be situations 
that arise in which people’s perceptions of the study 
design or implementation plan are not accurate, or their 
opinions and beliefs about the ethical issues associated 
with a study may not be in agreement with those of the 
research team and others involved in the study (e.g., the 
peer review panel, the IRB). Just as it is not 
unreasonable to expect differences in opinion on 
scientific approaches to an observational study, it is not 
unreasonable to expect differences of opinion on ethical 
approaches. The researchers, therefore, should be 
prepared to respond to criticism. The implementation 
plan and the communication plan should address how 
the research team should anticipate study elements that 
may be criticized. During study conceptualization, the 
research team should develop a list of potentially 
controversial study elements (many of which are 
discussed in this document). For each study element, the 
research team should describe how the ethical 
approaches to the study element were evaluated and 
selected. Both the process and the rationale for selection 
of a particular approach should be documented. At each 
step in the study planning and review process, the 


91 


research team should document discussions related to 
the specific element, considerations that were made, 
actions taken, and justification for the actions. Input 
from research team members, internal reviewers, 
external reviewers, community members, and others 
involved in the study should be documented for these 
controversial study elements. Similarly, for potentially 
controversial study elements, the review and actions by 
the IRB should be documented. All of this information 
should be compiled for potential use to prepare a set of 
Q&As that can be used by the research team and 
sponsoring organization to respond to criticism. When 
responding to criticism, establishing trust and credibility 
are essential, as discussed previously. The public’s 
perception of trust and credibility is determined by the 
public’s perceptions of the researchers’ knowledge and 
expertise, openness and honesty, and concern and care 
(Peters et al., 1997). These factors are important to 
consider in developing the information and approach 
that will be used to respond to criticism. 

There is a large volume of information available on 
“crisis communication” that the reader can use to 
develop a plan for anticipating and responding to 
criticism (e.g., FCN, 2001; ATSDR, 2007; U.S. HHS, 
2002). The key is to be proactive and have a plan before 
any criticism is raised. 

7.10 Responding to the Media, Public 
Inquiries, and Other Stakeholders 

Like crisis communications, the communication plan 
should include detailed plans for how to interact with the 
stakeholders, the media, and the public. Standard 
approaches have been developed for effective 
communications (e.g., the Federal Communicators 
Network's Communicators Guide [FCN, 2001]) with the 
media and will not be included in this document. A 
proactive plan, open and transparent communications, 
and easily to comprehend information will ensure 
effective communications with stakeholders and the 
public. 

References 

American Conference of Governmental Industrial Hygienists 
(ACGIH) (2008). TLV/BEI Resources. Available: 
http://www.acgih.org/tlv/ . 

Alderson P (1995). Will you help us with our research? Arch 
Dis Child 72(6):541-42. 

Anderson B, Hall B (1995). Parents’ perceptions of decision 
making for children. J Law Med Ethics 23(1): 15-9. 


ATSDR (Agency for Toxic Substances and Disease Registry) 
(2007). A Primer on Health Risk Communication Principles 
and Practices [online publication]. Available: 
http://www.atsdr.cdc.gov/risk/riskprimer/ [accessed 12 June 
2007]. 

CDC (Centers for Disease Control and Prevention) (2005). 
Third National Report on Human Exposure to 
Environmental Chemicals. National Center for 
Environmental Health, Atlanta, GA, NCEH Pub. No. 05- 
0570. Available: 

http://www.cdc.gov/exposurereport/pdf/thirdreport.pdf 

[accessed 12 June 2007], 

Covello V, Allen F (1988). Seven Cardinal Rules of Risk 
Communication. OPA-87-020. U.S. Environmental 
Protection Agency, Office of Policy Analysis, Washington, 
DC. Distributed by the Pennsylvania Dept, of 
Environmental Resources. Available: 

http://www.epa.gov/stakeholders/pdf/risk.pdf [accessed 12 
June 2007], 

Covello VT, McCallum DB, Pavlova M (eds) (1989). Effective 
Risk Communication: the role and responsibility of 
Government and Non-Government Organizations. New 
York. NY: Plenum Press. 

Covello V. Minamyer S, Clayton K (2007). Effective risk and 
crisis communication during w ater security' emergencies 
summary’ report ofEPA sponsored message mapping. 
EPA/600/R-07/027. National Homeland Security Research 
Center, Office of Research and Development, U.S. 
Environmental Protection Agency, Washington, DC. 
Available: 

http://www.epa.gov/nhsrc/pubs/reportCrisisCom040207.pdf 

FCN (Federal Communicators Network) (2001). 
Communicators Guide For Federal, State, Regional, and 
Local Communicators by the Federal Communicators 
Network. Available: 

http://www.publicforuminstitute.org/activities/20Q2/fcn/co 

mmguid.pdf [accessed 12 June 2007]. 

Fenske RA. Kissel JC, Lu C, Kalman DA, Simcox NJ, Allen 
EH, Keifer MC (2000) Biologically based pesticide dose 
estimates for children in an agricultural community. 

Environ Health Persp 108(6):515-20. 

Fernandez CV, Kodish E, Weijer C (2003). Informing study 
participants of research results: an ethical imperative. IRB 
25(3): 12-19. 

Health Canada (2006). The Strategic Risk Communications 
Framework. Available: 

http://www.riskcommunications.gc.ca [accessed 18 
September 2007], 


92 











IOM (Institute of Medicine) (2002). Responsible Research: A 
Systems Approach to Protecting Research Participants. 
Daniel D. Federman, Kathi E. Hanna, and Laura Lyman 
Rodriguez (eds). Washington, DC: The National Academies 
Press. 

Israel BA. Eng E, Schulz AJ, Parker EA (eds) (2005). 

Methods in Community-Based Participatory Research for 
Health. San Francisco, CA: Jossey-Bass. 

NIH (National Institutes of Health) (2005). Report and 
Recommendations on Public Trust in Clinical Research for 
the NIH Director from the Director’s Council of Public 
Representatives (COPR). National Institutes of Health, 
Director’s Council of Public Representatives, January 14, 
2005. Available: http://copr.nih.gov/reports/public trust.asp 
[accessed June 2007], 

Parkin RT (2004). Communications with research participants 
and communities: foundations for best practices. J Expo 
Anal Environ Epidemiol 14(7):516-23. 

Peters RG, Covello VT, McCallum DB (1997). The 
determinants of trust and credibility in environmental risk 
communication: an empirical study. Risk Anal 17(1 ):43-54. 

Stableford S and Mettger W (2007). Plain language: a 
strategic response to the health literacy challenge. J Public 
Health Pol 28:71-93. 

U.S. HHS (Department of Health and Human Services) 
(2002). Communicating in a Crisis: Risk Communication 
Guidelines for Public Officials, 2002. Available: 
http://www.riskcommunication.samhsa.gov/index.htm 

[accessed 13 June 2007]. 

U.S. EPA (U.S. Environmental Protection Agency) (2007). 
Drinking Water Contaminants. Environmental Protection 
Agency. Available: 

http://www.epa.gov/safewater/contaminants/index.html 

[accessed 13 June 2007]. 


Williams PR (2004) Health risk communication using 

comparative risk analyses. J Expo Anal Environ Epidemiol 
14(7):498-515. 

World Health Organization (2005). WHO Air Quality 
Guidelines Global Update 2005. Available: 
http://www.euro.who.int/Document/E87950.pdf [accessed 
13 June 2007]. 

Additional Information Resources 

Reckelhoff-Dangel C, Petersen D (2007). Risk Communi¬ 
cation in Action: The Risk Communication Workbook. 
EPA/625/R-05/003. National Risk Management Research 
Laboratory, Office of Research and Development, U.S. 
Environmental Protection Agency, Cincinnati, OH. 
Available: 

http://www.epa.gov/nnnrl/pubs/625r05003/625r05003.pdf 

[accessed 18 September 2007], 

U.S. EPA (U.S. Environmental Protection Agency) (2006). 
Considerations for Developing Alternative Health Risk 
Assessment Approaches for Addressing Multiple Chemicals, 
Exposures, and Effects. External Review Draft. 71 FR 
16306. 

U.S. EPA (U.S. Environmental Protection Agency) (2006). 
Paper on Tribal Issues Related to Tribal Traditional 
Lifeways, Risk Assessment, and Health and Well Being: 
Documenting What We’ve Heard. The National EPA-Tribal 
Science Council. Available: 
http://epa.gov/osp/tribes/tribal/TribalIssues.pdf . 

U.S. PHS (Public Health Service) (1995) Risk 
communication: working with individuals and communities 
to weigh the odds. Prevention Report. Feb/Mar. Available: 
http://odphp.osophs.dhhs.gov/pubs/prevrpt/Archives/95fml. 

htm. 


93 













































































Appendix A 


Additional Discussion of Observational and Exposure Terminology and 
Examples of Previous NERL Observational Human Exposure Studies 


The authors recognize that the words “observational 
human exposure studies” may convey a variety of 
meanings to different people. The word exposure is 
often interpreted differently by different people; 
similarly, the word observational may have a variety of 
interpretations. The following discussion regards 
potential meanings of those terms and describes what the 
authors of this document mean when they use the term 
observational human exposure studies. 

Exposure 

Exposure, as it is used throughout this document, is 
a technical term that is defined as the “contact of a 
chemical, physical, or biological agent with the outer 
boundary of an organism (e.g., a person) (U.S. EPA, 
1992). Exposure is quantified as the concentration of the 
agent in the medium in contact integrated over the time 
duration of that contact.” 



As the authors use the term, exposure is only the 
quantification of the “contact” as defined above. The 
word itself carries no connotation of intent, and it is not 
equivalent to intentional exposure, dose (dosing), or 


intentional dosing. A review of the dictionary definition 
of exposure shows that the word has many different 
meanings, and shades of meaning, in common, everyday 
English. However, when the authors use the word in this 
text it is being used in the technical sense that is defined 
above. 

The authors’ understanding of the word exposure is 
illustrated in Figure A-l. This graphic is a paradigm that 
ORD uses in formulating its human health research 
program. The graphic illustrates that exposure occurs at 
the intersection of both the chemical, physical, or 
biological agent and the person who is exposed. To 
understand exposure, one must understand the 
distribution of the “agent” throughout the environment 
over time and combine that understanding with 
knowledge about the location and activities of people 
that bring them into contact with the agent. Knowledge 
about the distribution of the agent in space and time 
generally involves measurements and data collection 
about environmental conditions external to the person. 
Knowledge about the person’s behaviors requires 
collection of personal information or observations of 
their location and activities. Understanding exposure, 
including the pathways, routes, duration, frequency, and 
magnitude of the exposure, requires combing both types 
of information. 

See the Glossary, Appendix F, for more information 
and the definition of additional and related terms. 

Observational 

Observational human exposure studies, as used in 
the context of this document, involve only the collection 
of environmental or biological samples and information 
for the purpose of quantifying the contact between the 
participant and the agent being studied. Observational 
human exposure studies are inherently the process of 
watching people in context—in their natural 
environment, doing routine activities—and collecting the 


95 


























samples and relevant information from them and from 
their surroundings to measure and calculate the 
exposures that occurred in the same context. 

Scientific Study Design: From a scientific study 
design perspective, an observational study of the sort 
being considered in this document is one where the 
researcher does not control the variables but, rather, 
observes both the variable and the outcome and tries to 
infer the relationship between the variable and the 
outcome. This contrasts with a controlled study where 
the researcher isolates and controls one or more 
variables in a systematic way to assess the impact of 
changes in the variables on an outcome measure. 
Consider the intervention study examples cited in the 
section on regulatory distinctions below (cleaning a 
house to reduce exposure in the residence and wearing a 
particle mask to reduce exposure to smoke from forest 
fires). In those cases, participants would be assigned 
either to receive the intervention (treatment) or not (the 
control group). The outcomes (exposures) would be 
measured and compared between the two groups to 
assess the effectiveness of the intervention. Similarly, 
drug trials would randomly assign participants to receive 
either a test medication or a placebo. The medical 
outcome (e.g., pain relief, blood pressure, cholesterol 
levels in blood) would then be measured for all 
participants, and the outcomes compared between the 
treated group (getting the test medication) and the 
control group (receiving the placebo). 

Controlled studies are often desirable in science 
because, when properly designed, they provide 
unambiguous estimates of the impact of unique variables 
on the outcome (even if the impact of one variable could 
normally be overwhelmed by other factors) and 
eliminate the need for alternate explanations of the 
experimental results (because other factors are held 
constant). However, controlled studies are not always 
possible. They may be unethical (e.g., to “treat” a group 
of women with abortions to test if there is a linkage 
between having had an abortion and breast cancer), 
impractical (e.g., to follow a cohort large enough to yield 
statistically significant results in a test of rare side 
effects to a medication), or just impossible to accomplish 
(e.g., to measure nutritional levels of a population in the 
middle of a war zone). 

As a consequence, much medical research is 
observational in the scientific sense being considered 
here. Public health data represent observations of health 
outcomes, but the factors that may have led to or 
influenced those outcomes are not under the control of 
any researcher. Observational techniques long have been 


used in medical studies to infer information about the 
impacts of certain factors on health outcomes. 
Commonly used techniques include cohort studies, case- 
control studies, cross-sectional studies, case reports, case 
series, and descriptive studies (NEAC, 2006; 
Vandenbroucke et al., 2007). 

Observational human exposure studies as used in 
this document are considered to be observational from a 
scientific study design perspective because the variables 
leading to exposure are not controlled by the researchers. 
Most of the observational human exposure studies 
conducted by NERL to date have been cross-sectional 
studies (sometimes repeated several times). While a 
particular variable may not be controlled by the 
researcher, the study design (e.g., selection of the 
population to be studied, location of the research, data 
selection to exclude confounding factors) can sometimes 
influence the range of values over which a variable may 
be observed. For example, NERL’s observational human 
exposure studies to understand exposure to PM (see 
www.epa.gov/heasd/sources/proiects_completed/pm pa 

nel studies.htm and www.epa.gov/heasd/sources/proiect 
s/a3a_understanding_airshed_sources.htm ) have 

traditionally excluded homes with smokers from the 
study population to avoid cigarette smoke as a 
confounding factor in the studies. 

Observational Studies in Market Research, 
Ethnography, and the Common Vernacular: 
Observational market research can involve covert 
observation, overt observation, or researcher 
participation. Covert observation is said to have a “key 
advantage” that “the respondent or consumer is unaware 
that they are being observed, allowing their behavior to 
be observed naturally” (see 

http://www.asiamarketresearch.com/glossary/observatio 

nal-research.htm ). This means that the subject’s behavior 
will be natural and uncontaminated by the researcher’s 
presence. On the other hand, covert observation may be 
construed to be deceitful and ethically questionable. 
Overt observations involve sampling surveys, polls, 
interviews, focus groups, etc. Validity of the data 
obtained this way may be shaded by people’s natural 
tendency to behave or respond ideally when they know 
they are being watched. Motorists routinely slow down 
when they think they are being observed by the police. 
Finally, the researcher may participate in the activity 
being observed. Ethnography is a long-term 
investigation of a group (often a culture) that is based on 
observations made while immersed in and, useually, 
participating in that group. “Ethnography provides a 
detailed exploration of group activity and may include 


96 









literature about and/ or by the group.” (See 
http://writing.colostate.edu/guides/research/observe/com 

3a 1 .cfm ). One obvious problem with immersion 
techniques is that the researcher may lose his or her 
objectivity. 

In the common language use of the term 
obsewational research , it appears to the authors that 
some people understand the term to imply that the 
observations are both benign and often covert, that is, 
without interaction with the persons being studied. That 
is not the case in NERL’s observational human exposure 
studies. The research often takes place in and around the 
homes of the participants. Often, the research involves 
asking the participant to answer a questionnaire and to 
provide personal samples (e.g., urine, blood). Collection 
of survey information and personal urine and blood 
samples cannot be done covertly, and collecting a blood 
sample is not considered to be benign. 

Observational Research in NERL: NERL’s 
observational human exposure studies entail the 
collection of environmental or biological samples, data, 
and information from study participants and their 
surroundings in their everyday environments, as they go 
about their normal activities, for the purpose of 
quantifying the contact between the participant and the 
agent being studied. As such, the studies are designed to 
meet the regulatory definition of observational research 
in the CFR. NERL’s studies also meet the scientific 
definition of an observational study, because the variable 
being studied, exposure to some agent, is not controlled 
by the NERL scientists. The observations are not covert, 
and they may or may not be noninvasive (e.g., 
sometimes blood samples may be collected). 

Because NERL’s observational human exposure 
studies meet the definition of human subjects research as 
set forth in the Common Rule, there is also a regulatory 
requirement to meet the ethical and scientific standards 
set forth in EPA’s human subjects regulations and in 
Agency rules. The research protocol must be evaluated 
and approved by an IRB and by EPA’s Human Studies 
Research Review Official (HSRRO) before any human 
subjects research effort can take place. But, even more 
compelling to NERL managers and scientists is the fact 
that NERL cannot conduct observational human 
exposure studies without the participation of willing 
individuals. Indeed, without the research participants, 
NERL’s human exposure research would be nothing. 
This intimate involvement of research subjects in 
NERL’s research imposes moral and ethical obligations 
to deal with participants respectfully and to ensure their 
safety, protection, and well-being. 


Regulatory Distinction Between Intentional 
Exposure and Observational Research 

Intentional Exposure: The CFR states, “Research 
involving intentional exposure of a human subject 
means a study of a substance in which the exposure to 
the substance experienced by a human subject 
participating in the study would not have occurred but 
for the human subject’s participation in the study” [40 
CFR 26.202(a)], This definition sets forth two 
requirements regarding an intentional exposure: (1) the 
exposure has to be to a substance that is being studied, 
and (2) at least one aspect of the exposure to the 
substance being studied has to be attributable to the 
subject’s participation in the study. 

The first requirement means the objective of the 
study must be to understand the impact or exposure of 
the substance being studied. In observational human 
exposure studies, like those that NERL conducts, the 
research protocol may require the use of isopropyl 
alcohol or some other chemical to collect a personal 
sample (e.g., to sterilize the puncture site immediately 
prior to collection of a personal sample of blood drawn 
by a trained phlebotomist). Indeed, it would be both 
unethical and bad medical practice not to sterilize the 
puncture site before drawing blood. But this requirement 
does not constitute intentional exposure because the 
research is not the study of isopropyl alcohol but of 
some other agent. Incidental exposures to chemicals like 
isopropyl alcohol still must be considered from a safety 
perspective, pass both scientific and ethical review, and 
be approved by the IRB, but such incidental exposures 
do not constitute intentional exposure. 

The second requirement is that the exposure as 
experienced by the subject “would not have occurred but 
for the human subject’s participation in the study.” The 
two primary ways in which intentional exposure studies 
commonly meet this definition are by the direct 
introduction of the study substance into the research 
environment under the control of the research protocol 
or by scripting the participants’ activities in such a way 
that their contact with the study substance is determined 
by the research. Although either would be sufficient to 
meet the regulatory definition, many, if not most, 
intentional exposure studies attempt to control both. 
Because “exposure is quantified as the concentration of 
the agent in the medium in contact integrated over the 
time duration of that contact,” intentional exposure 
studies are usually more scientifically robust if both the 
concentration of the agent and the duration of the 
exposure are controlled by the research. 


97 




Observational Research: In the language of the 
Code of Federal Regulations, “ observational research 
means any human research that does not meet the 
definition of research involving intentional exposure of 
a human subject' ’ (40 CFR 26.302). 

By this definition, observational research 
encompasses all human research that does not meet the 
definition of intentional exposure. As a consequence, it 
is a broad regulatory category that includes a variety of 
research domains, including human research that does 
not involve the study of exposures at all. This regulatory 
definition of observational is sufficiently broad, 
moreover, that it encompasses study types that this 
document is not intended to address. For example, it 
may be possible to design an intervention study that does 
not bring about or script in any way the participants’ 
exposure to a substance, but rather reduces or mitigates 
it. (Consider a study to test whether professional 
cleaning of the carpets, floors, walls, and other surfaces 
in a home might lead to a lower exposure to a residential 
contaminant or a study to determine if wearing a particle 
mask would reduce an individual’s exposure to smoke 
from forest fires.) Such a study might meet the 
regulatory definition of observational research (Note: 
The final decision in regard to whether any EPA study 
meets the definition of observational research resides 
with the Agency’s HSRRO), but it would not meet the 
authors’ intentions regarding “observational human 
exposure studies” as they are defined in this document. 
An intervention study, such as described in these two 
examples, does not involve observing people’s 
exposures in their everyday environments, as they go 
about their normal activities. In an intervention study, 
either the participant’s environment (cleaning of the 
household surfaces) or their behavior (wearing a particle 
mask) has been manipulated by the researcher. Secondly, 
the objective of these studies is not to understand 
exposures in everyday environments but would use 
changes in exposure to test the effectiveness of an 
intervention strategy. Such a study is not addressed in 
this document. 

Observational human exposure studies, as used by 
the authors of this document, generally meet the 
regulatory definition of observational research. But, not 
all studies meeting the CFR definition of observational 
research would be considered by the authors to be 
observational human exposure studies. 


Examples of NERL Observational 
Human Exposure Studies 

NERL and its predecessor organizations have 
conducted observational human exposure studies since 
1980. Table A-l lists many of those that NERL has 
conducted, supported, or participated in since 1980. The 
table gives the name of the study, dates, sample size, 
then type of study, a brief explanation of the research, 
and NERL's role therein. The table represents a variety 
of first-party or second-party research efforts. In many 
cases, NERL staff would design, oversee, and, if 
possible, participate directly in the study (first-party), 
but often contractor support would be needed to 
accomplish the field sampling or some of the sample 
analysis. In other cases, NERL researchers would solicit 
proposals for exposure research to be conducted to 
address specific exposure issues and then would fund 
researchers in academia or at nonprofit institutions to 
design and conduct the research (second-party research). 
In a few cases, grants might already be in place with 
research institutions, and NERL simply would augment 
the pre-existing funding to expand the exposure 
component (second-party). Some other cases involve 
research efforts initiated by other Federal agencies with 
which NERL would collaborate and participate in 
directly (first-party). 

An examination of the entries in the table shows that 
most of the agents being studied were chemicals, often 
air pollutants or pesticides. A few of the entries indicate 
that other agents, for example, molds and fungi or other 
microbes, were the subject of the study. The largest 
number of the studies involved small numbers of 
participants and often were designed to determine 
whether or not a method for collecting exposure-related 
data or samples was feasible or burdensome. Most of the 
smaller studies used convenience samples. Studies, like 
DEARS, CTEPP, NHEXAS, and TEAM, which 
involved large numbers of participants, employed 
randomized or probability-based approaches for 
selecting participants. 

Table A-2 shows the types of samples that often 
have been collected in NERL’s observational human 
exposure studies. Some of the samples, like air 
concentrations or surface wipes, allow NERL staff to 
determine the concentration of the studied chemicals in 
the environmental media with which the participants 
may come into contact. Other items, like time activity 
diaries or videotaping children to measure the amount of 
hand-to-mouth activity, allow NERL researchers to 
understand how people may come into contact with the 
agent and to estimate the duration or frequency of a 


98 












potential exposure. Still other measures, like personal 
samplers or biological samples, represent an attempt to 
determine a time-integrated measure of exposure. NERL 
staff put all of this information together to estimate an 
individual participant’s exposure, either through 
relatively direct measures of exposure or through 
algorithms that combine the media concentrations 
measurements and the activity data. 

References 

CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I 
Environmental Protection Agency Part 26 Protection of 
Human Subjects. U.S. Code of Federal Regulations. 
Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/ 
40cfr26_06.html [accessed 12 June 2007], 

NEAC (National Ethics Advisory Committee) (2006). Ethical 
Guidelines for Observational Studies: Observational 


research audits and related activities. Wellington, New 
Zealand: Ministry of Health. Available: 
http://www.neac.health.govt.nz/moh.nsf/indexcm/neac- 

resources-publications-ethicalguidelines . 

U.S. EPA (U.S. Environmental Protection Agency) (1992), 
Guidelines for Exposure Assessment. Environmental 
Protection Agency, Risk Assessment Forum, EPA/600/Z- 
92/001. Available: 

http://www.epa.gov/nceawwwl/raf/pdfs/exposure.pdf 

[accessed 1 May 2008]. 

Vandenbroucke JP, von Elm E, Altman DG, Gotzsche PC, 
Mulrow CD, et al. (2007). Strengthening the Report of 
Observation Studies in Epidemiology (STROBE): 
explanation and elaboration. PLoS Medicine 4(10): e297. 
doi: 10.1371/joumal.pmed.0040297. 


99 







Table A-1. Examples of Observational Human Exposure Studies Conducted or Funded by NERL 

or Its Predecessor Organizations 

Study 

Date 

Size 

Type 

Brief Description 

NERL Role 

Total Exposure 
Assessment 
Methodology 
(TEAM) Studies 

1980-1984 

400 

Households 

Three-stage 

stratified 

probability 

selection, 

cross- 

sectional 

The TEAM study was designed to develop and demonstrate 
methods to measure human exposure to toxic substances in 
air and drinking water. The goals were to develop methods to 
measure individual total exposure (from air, food, and water) 
and the resulting body burden of toxic and carcinogenic 
chemicals and to apply these methods within a probability- 
based sampling framework to estimate exposures and body 
burdens of urban populations in several U.S. cities. Air 
sampling measured personal exposure to airborne toxic 
chemicals in indoor air and in exhaled breath. Related 
objectives were to determine the relationships between 
personal, indoor, and outdoor, and blood, urine, and exhaled 
breath concentrations; determine the variability of VOC 
concentrations within a home; and determine seasonal and 
multiyear variability. The study was conducted in New Jersey, 
North Carolina, and North Dakota in three phases. 

EPA designed and 
run, contractor 
conducted 

Additional 

TEAM Studies 

1987 

51 in LA area, 
17 in NJ, 
and 75 in 
Baltimore 

Convenience 

sample 

A separate VOC TEAM study was carried out in Baltimore, 

MD: Baltimore lacks the petroleum and chemical 
manufacturing plants present in most of the previous TEAM 
study sites and is more representative of many U.S. cities. 
Focused studies were also conducted in New Jersey and Los 
Angeles to further explore the sources and factors 
contributing to personal VOC exposures identified in the 
earlier TEAM studies. 

EPA designed and 
run, contractor 
conducted 

Nonoccupationa 

1 Pesticides 
Exposure Study 
(NOPES) 

1986-1988 

259 

Probability 
selection, 
mainly cross- 
sectional, 
partly 

longitudinal 

First attempt to develop a methodology for measuring the 
potential exposure of the general population to common 
household pesticides using probability-based sampling; 
questionnaire data collection; and personal monitoring of air, 
drinking water, food, and dermal contact. Conducted in 
Jacksonville, FL, and Springfield and Chicopee, MA, to 
capture high- and low-pesticide-use areas, respectively. 

EPA designed and 
run, contractor 
conducted 

Nine-Home 
Children’s Pilot 
Study 

1990 

9 

Convenience 
pilot study 
to test 

methodology 

A 9-home pilot study was conducted to evaluate monitoring 
methods in the field that may be used to assess the potential 
exposures of children aged 6 months to 5 years to pesticides 
found in the home environment. Newly developed methods 
were tested for measuring pesticide residues in indoor air, 
carpet dust, outdoor soil, and on children's hands. Information 
also was collected on household characteristics, pesticides 
used and stored at the residence, and children's activities. 

EPA designed and 
run, contractor 
conducted 

Particle Total 
Exposure 
Assessment 
Methodology 
(PTEAM) Study 

1990 

178 

Probability 

A study of nonsmokers age 10 years and older in Riverside, 
CA, in which indoor, outdoor, and personal monitoring of 
integrated particle mass over 12-hour day and night periods 
was conducted for PM 10 and PM 25 . Polycyclic aromatic 
hydrocarbon and phthalate measurements were collected 
indoors and outdoors at a subset of 125 homes. A separate 
monitoring site provided ongoing 12-hour measurements of 
ambient particles throughout the study (48 days). Reference 
PM 10 and dichotomous samplers were used at this site in 
addition to personal and stationary monitors identical to those 
used for participant monitoring. Nighttime and daytime recall 
time-activity questionnaires, as well as household 
questionnaires, were administered to each selected subject 
and household, respectively, and meteorological and air 
exchange rate data were recorded for each monitored home. 

EPA designed and 
run, contractor 
conducted 

National Human 
Activity Pattern 
Study (NHAPS) 

1992-1994 

9,386 

Probability 

(national 

random 

dialing) 

This survey collected 24-hour activity diaries and other 
questionnaire data from participants from 48 states. It was 
conducted as a next-day telephone recall interview. 

EPA designed and 
run, contractor 
conducted 


100 

















Table A-1. (Continued) 

Study 

Date 

Size 

Type 

Brief Description 

NERL Role 

Agricultural 

Health Study 
(AHS) 

1993- 

present; 

PES 1999- 
2003 

84 applicators 
and a subset 
of family 
members in 

PES 

AHS survey 
is a 

longitudinal 
study of 
pesticide 
applicators in 
two states. 
PES, led by 
NERL, was a 
cross- 

sectional 

study. 

A large-scale, long-term ongoing study of Iowa and North 
Carolina pesticide applicators and farm families. This 
collaborative effort involving the National Cancer Institute 
(NCI), the National Institute of Environmental Health Sciences 
(NIEHS), the National Institute for Occupational Safety and 
Health (NIOSH), and the U.S. Environmental Protection 

Agency (EPA) examines how lifestyle habits, genetic factors, 
and agricultural exposures contribute to the risk of disease 
using questionnaire survey data from 89,658 participants. This 
is the largest, most comprehensive study of agricultural health 
ever conducted in the United States. The interagency exposure 
assessment study (Pesticide Exposure Study (PES)), led by 
NERL, was performed to assess exposures and exposure 
classification procedures used in the epidemiological study. 

Collaboration with 
other agencies; 
NERL led a 
contractor- 
conducted 
substudy called 
the Pesticide 
Exposure Study. 

The National 
Human 

Exposure 
Assessment 
Survey 
(NHEXAS)— 
Overview 

1995-1998 

See specifics 
in entries 
below. 


A Federal interagency research effort coordinated by EPA and 
consisting of four demonstration studies using probability- 
based sampling designs conducted in partnership with other 
Federal agencies (CDC, FDA, and NIST), universities, and 
research institutions. Household environmental and personal 
samples were collected and questionnaires were administered. 
Biological media, including blood and urine, also were sampled 
and monitored for parent contaminants or their metabolites. 

The studies were undertaken to evaluate total human exposure 
to multiple chemicals on a community and regional scale with 
the following aims: provide a baseline of the normal range of 
exposure to chemicals in the general population; identify 
subgroups of the general population that are likely to be highly 
exposed; and evaluate and improve the accuracy of models 
developed to predict exposure to chemicals. 

EPA oversaw 
general design for 
the research, then 
solicited, evaluated 
and funded the 
individual studies 
(see below). 

Details of research 
were established 
by recipients. 

NHEXAS- 

Arizona 

1995-1998 

179 

Households 

Probability, 

cross- 

sectional 

The NHEXAS-Arizona study sampled residences determined 
by a population-based probability research design for the total 
population of Arizona and measured metals, pesticides, and 
volatile organic compounds (VOCs). The study was conducted 
by a consortium composed of the University of Arizona, 

Battelle Columbus, and the Illinois Institute of Technology. 

Designed and 
conducted by 
award recipient 
(see above). 

NHEXAS- 

Maryland 

1995-1996 

80 

Households 

Probability, 

longitudinal 

The study sampled residences of Baltimore and four adjacent 
counties and measured metals, pesticides, and polycyclic 
aromatic hydrocarbons (PAHs). Data collection occurred up to 

6 times over 1 year for each of the participating households. 

The study was conducted by Harvard University, Emory 
University, Johns Hopkins University, and Westat. The study 
investigated temporal variability in multimedia, multipollutant 
exposures. 

Designed and 
conducted by 
award recipient 
(see above). 

NHEXAS- 
Region 5 

1995-1997 

250 

Households 

Probability, 

cross- 

sectional 

The Region 5 study was conducted in EPA’s Region 5 (Ohio, 
Michigan, Illinois, Indiana, Wisconsin, and Minnesota), and 
included personal exposure, residential concentration, and 
biomarker measurements of metals and VOCs. The study was 
conducted by the Research Triangle Institute (RTI) and the 
Environmental and Occupational Health Sciences Institute 
(EOHSI). 

Designed and 
conducted by 
award recipient 
(see above). 

Minnesota 
Children's 
Pesticide 
Exposure Study 
(MNCPES) 

1997 

102 Children 

Probability, 

cross- 

sectional 

Multimedia study of children 3-13 years conducted in 

Minnesota to evaluate children's pesticide exposure in urban 
and rural areas. The study provides exposure, environmental, 
and biologic data relating to multipathway exposures of 
children for four primary pesticides (chlorpyrifos, malathion, 
diazinon, and atrazine), 14 secondary pesticides, and 13 
polynuclear aromatic hydrocarbons (PAHs). This study 
complements and extends the populations and chemicals 
included in the NHEXAS-Region 5 study. 

Designed and 
conducted by 
award recipient 
(see above). 


101 



















Table A-1. (Continued) 

Study 

Date 

Size 

Type 

Brief Description 

NERL Role 

Particulate 

Matter (PM) 

Panel Studies 

1998-2001 

200 

Individuals 
(5 to 63 per 
study) 

Longitudinal 

A series of longitudinal studies in a number of U.S. cities 
conducted by EPA or by organizations sponsored through the 
National Exposure Research Laboratory (NERL). A primary 
goal was to determine the relationships between personal 
exposures to particles and associated gases relative to 
stationary outdoor monitor concentrations in high-risk 
subpopulations and to identify human activity patterns that 
might contribute to personal exposure. The investigators varied 
study locations, monitoring seasons, and study populations. 
Susceptible subpopulations of interest included chronic 
obstructive pulmonary disease (COPD) patients, individuals 
with cardiovascular disease, the elderly, asthmatics, and 

African Americans with hypertension. Panels of healthy 
individuals also were included. Because the elderly is the 
subpopulation most sensitive to health effects associated with 
PM exposures, the majority of subjects were over age 65. 

NERL conducted 
one panel study 
with contractor 
support; funded 
and collaborated 
on others with 
Harvard School of 
Public Health, 
University, of 
Washington, and 
NYU. 

Dietary Intake of 
Young Children 
(DIYC) 

1999-2000 

3 Homes 

Convenience 

Performed in the Raleigh, NC, area in homes with children 1 to 

3 years old. Homeowners reported either professional or self 
applications of diazinon. Goals of the study were to evaluate 
methods to measure excess dietary exposures resulting from 
food-handling activities by young children during eating and to 
assess whether the Children's Dietary Intake Model (CDIM) 
accurately represents total dietary exposures of children. Study 
resulted in refinements of model parameters for transfer and 
activity. 

NERL designed, 

contractor 

conducted 

Children’s 
Pesticide Post- 
Application 
Exposure Study 
(CPPAES) 

1999-2001 

10 Homes 

Convenience, 
multiday pilot 
study to test 
methodology 

Observational measurement study of exposure to chlorpyrifos 
among children 2-5 years of age in urban New Jersey homes 
following crack and crevice treatment by a professional 
applicator. Study investigated decay of pesticide levels over 
time, transfer of pesticide from microenvironmental media to 
child, and factors that affect transfer. Dermal transfer evaluated 
with surface wipes, hand wipes, dermal wipes, cotton 
garments, and videotaping. 

NERL funded the 
Environmental and 
Occupational 

Health Sciences 
Institute (EOHSI). 

Develop Risk 
Assessment and 
Define Some 

Risk 

Management 
Options for 
Exposure of 
Children to Toxic 
Mold Using 
Stachybotrys 
chartarum as an 
Example 

2000 

8 cases and 

8 controls 

Case control 
study 

Physicians at Case-Western Reserve treating children with 
idiopathic pulmonary hemorrhage evaluated the nature of the 
fungus found in homes of the afflicted and control children to 
determine if Stachybotrys was a potential factor in the illness. 
Three of the 8 cases, and none of the controls, had 

Stachybotrys strains that potentially were implicated. 

NERL staff 
collaborated with 
Case-Western 
Reserve University 
by conducting lab 
analysis for 
Stachybotrys. 

Children’s Total 
Exposure to 
Persistent 
Pesticides and 
Other Persistent 
Organic 
Pollutants 
(CTEPP) 

2000-2001 

257 

Households 

Randomized, 

cross- 

sectional 

The largest children's exposure study undertaken to date. It 
examines aggregate exposures of children 18 months to 5 
years to pollutants commonly found in everyday environments. 
The major objectives were to quantify children’s aggregate 
exposures, apportion exposure pathways, and identify 
important exposure media. Participants were recruited from 12 
urban and rural counties in North Carolina and Ohio using a 
random digit dialing method. Monitoring was performed at both 
daycare centers and homes. Samples collected include food, 
beverages, indoor air, outdoor air, hand wipes, dust, soil, 
transferable residues, floor and surface wipes, and urine. The 
samples were analyzed for more than 40 pollutants, including 
insecticides, phthalate esters, phenols, polychlorinated 
biphenyls, and PAHs. 

NERL designed, 

contractor 

conducted 

Car-Related 

Occupational 

PM and Air 
Toxics Exposure 
to Patrolmen 
Study (COPP) 

2001 

9 

Convenience, 

longitudinal 

Scientists monitored air pollutants inside and outside vehicles 
of healthy highway patrol officers in North Carolina while 
troopers were on patrol for 9-hour shifts and examined 
cardiovascular effects. The findings indicated that people 
driving in motor vehicles are exposed to PM 2 5 and other 
pollutants generated from motor vehicles, and that these 
exposures appear to cause cardiovascular changes. 

EPA designed and 
conducted with 
contractor support 


102 
















Table A-1. (Continued) 

Study 

Date 

Size 

Type 

Brief Description 

NERL Role 

First National 
Environmental 
Health Survey of 
Child Care 
Centers (CCC) 

2001 

168 Child care 
centers 

Probability- 
based 
selection on 
national scale 

A collaborative study with the Department of Housing and 

Urban Development (HUD) and the Consumer Product Safety 
Commission (CPSC) of pesticide use and young children’s 
(less than 6 years old) potential exposure to pesticides and 
other pollutants in institutional childcare centers. This national 
study used multistage sampling with clustering. Indoor wipe 
and outdoor soil samples were analyzed for pesticides, lead, 
and allergens (mold/fungi). Pesticide use practices and 
application information were obtained from the commercial 
pest control applicators serving the centers. 

HUD and CPSC 
study. NERL 
collaborated and 
conducted analysis 
of molds/fungi and 
helped with lead 
and pesticide 
measurements. 

A Pilot Study 
Examining 
Translocation 
Pathways 
Following a 
Granular 
Application of 
Diazinon to 
Residential 

Lawns(PET) 

2001 

6 Households 

Convenience, 
multiday pilot 
study to test 
methodology 
for exposure 
measure¬ 
ments 

Observational pilot exposure measurement study of residential 
exposures after homeowner had routinely applied granular 
formulation diazinon-containing turf treatment to residential 
lawns. Study was performed near Raleigh, NC, and was 
preceded by a 1-home methodology feasibility study. Purpose 
was to evaluate methods for assessing pet-borne transfer, 
translocation and exposure pathways, and decay rates. 

EPA conducted 
with contractor 
support 

Biological and 
Environmental 
Monitoring for 
Organo- 
phosphate and 
Pyrethroid 
Pesticide 
Exposures in 
Children Living 
in Jacksonville, 

FL (JAX) 

2001 

9 Households 
in NERL 
exposure 
component 

Convenience, 

cross- 

sectional 

The objectives of this investigation in Jacksonville, FL, were to 

(1) assess organophosphate (OP) and pyrethroid pesticide 
exposures in a group of 4- to 6-year-old children from 
Jacksonville by measuring the urine metabolite levels, 

(2) identify possible sources of these pesticides through 
screening measurements and pesticide inventories, and 

(3) examine the relationship between environmental and 
biological levels. The Duval County Health Department 
(DCHD) collected urine samples for CDC from 200 children 
visiting six public health clinics in Jacksonville, and collected 
environmental screening samples at approximately 25% of 
these children’s homes. A detailed aggregate exposure 
assessment at 9 homes was overseen by NERL and involved 
collection of surface wipes, transferable residues, air, duplicate 
diet, cotton garment samples, and urine samples. A time- 
activity diary of the children’s activities was included. 

Multiagency effort; 
NERL was a 
participant and led 
the 9-home 
exposure 
component. 

Exposure 

Assessment for 

Community- 

Acquired 

Legionnaires 

Disease 

2001 

21 

Case-control 

Work with Veteran’s Administration hospital staff. Cases of 
Legionnaires Disease were evaluated for potential for 
exposure from residential drinking water taps. In about 24% of 
the tested cases, homes were found to have Legionella 
bacteria in water taps at home, compared to their absence in 
other cases and in controls 

NERL funded IAG 
with VA to conduct 
study. 

Center for the 
Health 

Assessment of 
Mothers and 
Children of 
Salinas 
Quantitative 
Exposure 
Assessment 
Study 

(CHAMACOS) 

2002 

20 Children 

Convenience 

Incidental pesticide exposure measurement study of 
farmworkers’ children ages 5 to 35 mo. Purpose is the 
evaluation of methods for aggregate exposure measurements 
and the evaluation of pathways of exposure and important 
factors that affect exposure. Measurements include pesticide 
distributions in microenvironments where children spend time, 
transfer of pesticides from microenvironmental media to child, 
and factors that affect transfer. 

EPA grant to UC 
Berkeley; NERL 
augmented the 
existing research 
effort. 

Feasibility of 
Macroactivity 
Approach To 
Assess Dermal 
Exposure 
(Daycare) 

2002 

9 Daycare 
centers 

Convenience 

Study identified daycare centers with previously established 
contracts for routine monthly pesticide applications and 
conducted screening sampling in each to evaluate the 
distributions of transferable pesticide residues on floor surfaces 
where children spend time. One daycare was selected for 
intensive measurements, and children from different age 
groups volunteered to wear full-body cotton suits for short time 
periods while their activities were videotaped. 

NERL designed, 

contractor 

conducted 


103 















Table A-1. (Continued) 

Study 

Date 

Size 

Type 

Brief Description 

NERL Role 

Tampa 

Asthmatic 
Children's Study 
(TACS) 

2002 

9 Residences 

Convenience 
sample, pilot 
study to test 
methods. 

Pilot study on methods for measuring personal, indoor 
residential, outdoor residential, and ambient combustion- 
related products, particulate matter, and air toxics. The study 
identified microenvironmental factors affecting penetration of 
pollutants into homes and reduction of exposures to pollutants 
for asthmatic children (0-5 years of age). 

NERL designed, 

contractor 

conducted 

Pilot Study To 
Evaluate Data 
Collection 
Methods for 
Young 

Children’s and 

Household 

Activities 

2004 

3 Homes 

Convenience, 
pilot study to 
test 

methodology 

Pilot aggregate exposure study of three homes to assess 
burden of alternative exposure sample collection methods. 

NERL designed, 

contractor 

conducted 

Detroit Exposure 
and Aerosol 
Research Study 
(DEARS) 

2004-2007 

150 

Randomized 

household 

selection with 

qualification 

criteria; 

longitudinal 

Recruitment from seven distinct neighborhoods in Detroit 
required strong community relations and partnership with State 
and local organizations. This study monitored for air pollutants 
at the personal level and evaluates how well centrally located 
(ambient) monitors represent exposure at the residential and 
personal level. Sampling is for 5 days duration in summer and 
again in winter. 

NERL designed 
and run; with 
contractor support 
and collaborators 
such as the 
University of 
Michigan 

Accelerometer 
Pilot Study 

2004 

9 

Convenience, 
pilot study to 
test 

methodology 

Nine children <24 months old and their primary caregivers 
participated in this study to (a) determine if very young children 
will wear an accelerometer for relatively long periods of time 
and comply with the protocol for its use, (b) evaluate how well 
a caregiver can estimate the activity level of his/her infant or 
toddler when completing an exposure-oriented time-activity 
diary, and (c) compare accelerometer count output with 
caregiver-provided estimates of children's activity level. 

NERL designed 
and run, with 
contractor support 

Pilot Study of 

Waterborne 

Infections 

2005 

1296 

Convenience, 
all volunteers 
from 

community 
using public 
water supply 

Measure antibodies in people’s saliva for antibodies to 
Cryptosporidium , Noroviruses, Rotaviruses, Helicobacter 
pylori , and Toxoplasma gondii before and after installation of 
an ultraviolet treatment system for a public water supply. Also 
served as test of methodology for detecting people's prior 
exposure to infectious agents. 

EPA planned 
research (NERL is 
a collaborator), 
contractor 
conducted 


104 
















Table A-2. Types of Samples Collected in NERL Observational Human Exposure Studies 

Samples or Data 

Exposure Concern and Typical Type of Analysis 

Environmental Media 

Air pollutants 

Air pollutants being inhaled. Collect samples from central site, outside residence, and inside residence to assess 
pollutants in various locales. Measure gaseous and particle-bound pollutants. 

Soil 

Estimate track in and subsequent dermal or inhalation contact. Analyze for metals, pesticides, etc. 

House dust 

Dust from carpets and floors that may result in dermal contact or reentrainment and inhalation. Analyze for 
pesticides, metals, and tracers of outdoor sources. 

Surface wipes 

Dermal contact, children’s hand to mouth, and contact with food and subsequent ingestion. Analyze for metals and 
pesticides. Examine eating and food preparation areas too. 

Transferable residues 

Similar to surface wipes, using a surrogate for the transfer from the surface to the skin. 

Duplicate diet 

Use to assess ingestion exposures from food. Exact duplicate of amount and items eaten by participant and 
analyzed for pesticides, metals, etc. Includes drinking water samples as part of diet or other beverages consumed. 

Handled food 

Finger foods like cheese or luncheon meets that have been prepared and processed identically to foods children 
might eat to evaluate how much pollution may be removed from surfaces and ingested with the food. 

Human Activity Data 

Time-activity diaries 

Recall diaries to account for all times and activities in a day. Information includes location and activities. 

Activity loggers 

Device used to assess the nature of a person's activities. Portable nephelometers have been used to keep up with 
people’s activities by showing when they were near PM sources. Accelerometers to measure level of activity of 
children at play. GIS and inertial devices to try to measure locations as a function of time of day. 

Questionnaires 

Query participants about things like daily activities for themselves or their children; housing characteristics; 
participant characteristics, including occupation, diet, smoking habits, hobbies, etc.; and recent use of pesticides or 
other consumer products. 

Videotaping 

Use videos to measure frequency and duration of mouthing activities in children. 

Household inventories 

Inventory consumer products in house. Use items to ask about usage frequency and history. 

Researcher observations 

Information about open doors and windows (air exchange), heating and cooking sources, pets, and other activities 
that may lead to potential exposures may be observed. 

Personal or Biological Samples 

Urine 

Urinary excretion of pollutants and their contaminants give important information about the nature of prior 
exposures and their magnitude. 

Personal air monitors 

Individual wears samplers on his/her person while going about normal activities to measure pollutants in breathing 
zone of individual. 

Hand wipes 

Hand wipes remove contaminants from skin surface. Analyze for pesticides, metals, organic chemicals, and use 
values to estimate dermal exposure and hand-to-mouth ingestion of pollutants. 

Dermal surrogates 

Participant may wear cotton garments or socks as a collector. Clothing is analyzed for pesticides, metals, organic 
chemicals, etc. Measured contaminant quantities are used to estimate potential for dermal exposure. 

Saliva samples 

Test for antibodies to infectious agents, suggesting prior exposure and infection by microbial agent. 

Blood 

Some epidemiological studies that NERL scientists have collaborated on have collected blood samples. 


105 























































































Appendix B 


The Process for Development of This Document: 
Description of the Expert Panel Workshop (November 28 and 29, 2006), 
the External Peer Review by the HSRB (October 21-24, 2007), 

and Public Comment 


Expert Panel Workshop 

An Expert Panel Workshop was convened in 
Durham, NC, on November 28 and 29, 2006. An ad hoc 
panel of experts was assembled to discuss issues 
associated with the preparation of this document prior to 
beginning its first draft. The workshop was coordinated 
by ERG, Inc., who was also responsible for compiling 
information from the workshop in a final workshop 
report, available on the Scientific and Ethical 
Approaches for Observational Exposure Studies 
(SEAOES) Web site at www.epa.gov/nerl/sots . 

The charge to the Expert Panel Workshop members 
was as follows. 

The panel is asked to consider these issues prior to 
the workshop in preparation for discussion during 
this workshop meeting: 

1. Provide recommendations on the content and 

organization of the document. 

a. Identify the major scientific and ethical 

areas/issues in the design and 

implementation of observational human 
exposure measurement studies that should 
be considered for inclusion in the document. 

b. Identify specific elements in each of these 
major areas that should be considered for 
inclusion in the document. 

c. Provide recommendations on the type and 
level of information that should be 
considered for inclusion in the document 
when describing state-of-the-science 
approaches, methods, techniques, or 
standards. 

d. Provide recommendations on the criteria 
that should be considered when evaluating 
and identifying the state-of-the-science for 


the approaches, methods, techniques, or 
standards. 

2. Provide recommendations and listings of sources 
of information for developing the document 
including case studies where available. 

3. Identify at least ten specific elements of the 
design and implementation of these studies that 
the panel considers to have the most uncertainty 
with regard to the “state-of-the-science,” discuss 
these elements, and provide recommendations on 
state-of-the-science approaches for them. 

The following individuals were members of the Expert 
Panel. 

Timothy Buckley (Chair) 

Division of Environmental Health Sciences 
School of Public Health 
Ohio State University 
Columbus, OH 

Sophie Balk 

Attending Pediatrician 
Children’s Hospital at Montefiore 
Professor of Clinical Pediatrics 
Albert Einstein College of Medicine 
Bronx, NY 

David Carpenter 

Director, Institute of Health and Environment 
University of Albany, SUNY 
Rensselaer, NY 


107 




Giselle Corbie-Smith 

Department of Social Medicine 
University of North Carolina 
Chapel Hill, NC 

Alan Fleischman 

Senior Advisor 

The New York Academy of Medicine 
New York, NY 

Natalie Freeman 

Center for Environmental and Human Toxicology 
Department of Physiological Sciences 
University of Florida 
Gainesville, FL 

Loretta Jones 

Healthy African American Families 
Los Angeles, CA 

Bruce Lanphear 

Professor of Pediatrics and of Environmental Health 
Division of General and Community Pediatrics 
Cincinnati Children’s Hospital Medical Center 
Cincinnati, OH 

Michael Lebowitz 

Arizona Health Sciences Center 
Colleges of Public Health and Medicine 
University of Arizona 
Tucson, AZ 

Jerry Menikoff 

Department of History and Philosophy of Medicine 
University of Kansas Medical Center 
Kansas City, KS 

Rebecca Parkin 

Associate Dean for Research and Public Health Practice 
Professor of Environmental and Occupational Health 
School of Public Health and Health Service 
George Washington University Medical Center 
Washington, DC 


Review by the EPA Human Studies Review 
Board and Public Comment 

The process for developing this document included 

the following steps after the Expert Panel Workshop. 

• A draft document was written by NERL researchers. 

• The draft document was distributed to internal EPA 
staff for review and comment (see Acknowledgements 
for the list of reviewers). 

• The draft document was revised to address internal 
reviewer comments; an external review draft 
document was prepared. 

• The availability of the external review draft document 
for public comment was announced in a Federal 
Register notice. 

• An EPA docket was opened, and the external review 
draft document was available for public comment for 
45 days. 

• The external review draft document also was provided 

to EPA’s Human Studies Review Board (HSRB) for 
review and comment (see 

http://www.epa.gov/osa/hsrb/ for information on the 
HSRB). 

• The review by HSRB was announced in a Federal 
Register notice. 

• HSRB met October 21-24, 2007, and discussed the 
document during the meeting. 

• HSRB provided EPA with comments on the document 
in their final report of the October meeting. 

The charge to the HSRB for the SEAOES document 

review was that shown just below. 

Draft Document on Scientific and Ethical 
Approaches for Observational 
Exposure Studies 

Charge to the Human Studies Review Board 
(October 4, 2007) 

Observational human exposure studies are 
performed to collect information about individuals 
and the environment around them in order to better 
understand people’s exposures. These studies 
typically involve measurements of chemicals in the 
food people eat, the water they drink, the air they 
breathe and dust on the surfaces they touch. In 
addition, information about the study participants and 
their homes, work environments and activities are 
collected, as well as biomonitoring samples. It is 
important to understand why and how people are 
exposed to chemicals in the environment for EPA to 
fulfill its mission to protect human health. 


108 



EPA scientists and their managers take the 
protection of human subjects who participate in their 
observational studies very seriously. The steps 
needed to ensure protection of the human subjects are 
often complex, and the specific actions will vary 
depending on the objectives of the study, details 
about the participants, and the communities in which 
the studies are performed. 

This document is intended as a resource and 
reference for scientists in EPA’s Office of Research 
and Development (ORD) National Exposure 
Research Laboratory (NERL) as they develop and 
implement observational human exposure studies. 
The authors recognize that this document may also 
prove to be useful to others involved in exposure 
science research, but the document is not meant to 
represent an official Agency “guidance document” 
and should not be used that way. This document does 
not provide solutions to the scientific and ethical 
issues that will undoubtedly arise as such studies are 
undertaken: no document could provide all of the 
answers in advance or develop a comprehensive 
checklist for all such studies. Rather, this document 
attempts to identify the types of issues that will need 
to be considered and addressed as NERL researchers 
plan and implement observational human exposure 
studies. The researchers will need to work with others 
- the study team, IRB members, EPA Human 
Subjects Research Review Official (HSRRO), the 
participants and their community, and other 
stakeholders - to identify and address all of the 
relevant issues for their particular study in order to 
ensure that the specific elements of the study will 
safeguard and protect the human research subjects. 


Charge to the Human Studies Review Board 
The draft document on Scientific and Ethical 
Approaches for Observational Exposure Studies 
consists of the following seven sections: 

1. Introduction 

2. Elements to be Considered in Study 
Conceptualization and Planning 

3. Ensuring Protection of Vulnerable Groups 

4. Privacy, Confidentiality, and Other Concerns 
Related to Observational Human Exposure 
Measurement Studies 

5. Creating an Appropriate Relationship Between 
Participant and Investigator 

6. Building and Maintaining Appropriate Community 
and Stakeholder Relationships 

7. Designing and Implementing Strategies for 
Effective Communication 

The Human Studies Review Board is asked to 
address the following questions for each section of 
the draft document: 

1. One of the goals of the document is identify the 
major scientific and ethical areas and issues that 
researchers should address in the design and 
implementation of observational human exposure 
measurement studies, with the emphasis on the 
areas requiring ethical considerations. Does each 
section identify the major areas and issues where 
ethical considerations should be addressed? 

2. The document is intended to serve as a reference 
and resource of information that researchers can 
use in the design and implementation of 
observational exposure studies. For each section, 
are there additional sources of information that 
should be considered for inclusion? 

3. Is the information presented accurately and clearly 
in each section? 


109 







Appendix C 

Recommended Content of a Human Subjects Protocol 


The Council for International Organizations of Medical 
Sciences (CIOMS, 2002) has developed a comprehensive 
list of items that they recommend for inclusion in a 
human subjects research protocol. Many of the items 
that they identify are also useful for observational human 
exposure studies. 

Items Relevant to Observational Human 
Exposure Studies 

(1) The title of the study 

(2) A summary of the proposed research in lay or 
nontechnical language 

(3) A clear statement of the justification for the study 

(4) The investigators’ views of the ethical issues and 
considerations raised by the study and, if 
appropriate, how it is proposed to deal with them 

(5) A summary of previous studies on the research 
problem, including unpublished studies known to 
the investigators, and information on previously 
published research on the topic 

(6) A statement that the principles of the Belmont 
Report and requirements specified in 40 CFR 26 
will be implemented 

(7) An account of previous submissions of the protocol 
for ethical review and their outcomes 

(8) A brief description of the sites where the research is 
to be conducted, including information about the 
adequacy of facilities for the safe and appropriate 
conduct of the research, and relevant demographic 
and epidemiological information about the 
population to be studied 

(9) The names and addresses of the funding 
organization, research partners, and collaborators 

(10) The names, addresses, institutional affiliations, 
qualifications, and experience of the principal 
investigator and other investigators 


(11) The objectives of the study, its hypotheses or 
research questions, its assumptions, and its 
variables 

(12) A detailed description of the design of the study 

(13) The number of research subjects needed to achieve 
the study objective, and how this was determined 
statistically 

(14) The criteria for inclusion or exclusion of potential 
subjects and justification for the exclusion of any 
groups on the basis of age, sex, social or economic 
factors, or other reasons 

(15) The justification for involving as research subjects 
any persons with limited capacity to consent or 
members of vulnerable social groups and a 
description of special measures to minimize risks 
and discomfort to such subjects 

(16) The process of recruitment (e.g., advertisements) 
and the steps to be taken to protect privacy and 
confidentiality during recruitment 

(17) A description and explanation of any and all 
interventions 

(18) The measurements to be performed in the study, 
including environmental and biological sample 
collection, and other data and information that will 
be collected 

(19) If applicable, clinical and other tests involving the 
study participants that are to be carried out 

(20) The rules or criteria according to which subjects 
may be removed from the study or the study may be 
terminated 

(21) The methods of recording and reporting adverse 
events or reactions, and provisions for dealing with 
complications 

(22) The potential benefits of the research to subjects 
and to others 

(23) The expected benefits of the research to the 
population, including new knowledge that the study 
might generate 


111 



(24) The means proposed to obtain individual informed 
consent and the procedure planned to communicate 
information to prospective subjects, including the 
name and position of the person responsible for 
obtaining consent 

(25) When a prospective subject is not capable of 
informed consent, satisfactory assurance that 
permission will be obtained from a duly authorized 
person, or, in the case of a child who is sufficiently 
mature to understand the implications of informed 
consent but has not reached the legal age of 
consent, that knowing agreement, or assent, will be 
obtained, as well as the permission of a parent, or a 
legal guardian or other duly authorized 
representative. 

(26) An account of any economic or other compensation 
or incentives to prospective subjects to participate, 
such as offers of cash payments, gifts, or free 
services or facilities, and of any financial 
obligations assumed by the subjects, such as 
payment for medical services 

(27) The plans and procedures and the persons 
responsible for communicating to subjects 
information arising from the study (on harm or 
benefit, for example) or from other research on the 
same topic that could affect subjects’ willingness to 
continue in the study 

(28) The plans to inform subjects about the results of the 
study 

(29) The provisions for protecting the confidentiality of 
personal data and respecting the privacy of subjects, 
including the precautions that are in place to 
prevent disclosure of the results of a subject’s 
genetic tests to immediate family relatives without 
the consent of the subject 

(30) Information about how the code, if any, for the 
subjects’ identity is established; where it will be 
kept; and when, how, and by whom it can be broken 
in the event of an emergency 

(31) Any foreseen further uses of personal data or 
biological materials 

(32) A description of the plans for statistical analysis of 
the study, including plans for interim analyses, if 
any, and criteria for prematurely terminating the 
study if necessary 

(33) A list of the references cited in the protocol 

(34) The source and amount of funding of the research, 
including the organization that is sponsoring the 
research and a detailed account of the sponsor’s 
financial commitments to the research institution. 


the investigators, the research subjects, and, when 
relevant, the community 

(35) The arrangements for dealing with financial or 
other conflicts of interest that might affect the 
judgment of investigators or other research 
personnel, including informing the institutional 
conflict-of-interest committee of such conflicts of 
interest; the communication by that committee of 
the pertinent details of the information to the ethical 
review committee; and the transmission by that 
committee to the research subjects of the parts of 
the information that it decides should be passed on 
to them 

(36) The time schedule for completion of the study 

(37) Particularly in the case of an industrial sponsor, a 
contract stipulating who possesses the right to 
publish the results of the study and a mandatory 
obligation to prepare with and submit to the 
principal investigators the draft of the text reporting 
the results 

(38) The circumstances in which it might be considered 
inappropriate to publish findings, such as when the 
findings of any study may present risks to or 
stigmatize the interests of a community or 
population or of a racially or ethnically defined 
group of people 

(39) A statement that any proven evidence of 
falsification of data will be dealt with in accordance 
with the policy of the sponsor to take appropriate 
action against such unacceptable procedures 

Source: CIOMS (The Council for International Organizations of 

Medical Sciences) (2002). International Ethical Guidelines for 

Biomedical Research Involving Human Subjects. World Health 

Organization. Geneva, Switzerland. 


112 


Appendix D 

Recommendations for Enhancing Public Trust 


Although the Report and Recommendations on Public 
Trust in Clinical Research for the NIH Director from the 
Director’s Council of Public Representatives (COPR) 
was developed in the context of NIH-supported clinical 
research, many of the recommendations are applicable to 
observational human exposure studies. A summary of 
recommendations from the report is provided below. 

Building Trust Through Community 
Partnerships 

Recommendation 1: Incorporate into the NIH 
mission and philosophy that it values the involvement 
of the community in research and create language 
that expresses this value. 

Recommendation 2: Encourage change in the 
culture of the scientific community to ensure that 
medical research is viewed in the context of a long¬ 
term commitment to the community, not a one-time 
research study. 

Recommendation 3: Investigate ways to provide 
mechanisms that allow for follow-up health care 
when a clinical trial or treatment ends. 

Building Relationships with Patients 
(Participants) (True partnerships with 
patients may not be possible, but 
bidirectional relationships must be 
enhanced.) 

Recommendation 4: Educate and reorient the 
current research community to the importance of 
treating the public as a partner in the research 
process. 

Recommendation 5: Set the expectation across 
the entire research community, NIH funded research 
and beyond, that study results and outcomes should 
be shared with the research participants and the larger 
community promptly and consistently. This will 
ensure translational research. 

Building Partnerships with Community 
Providers 

Recommendation 6: Take action to interest 
community providers in clinical research and 


maintain their involvement. 

Recommendation 7: Provide incentives (not just 
financial) for primary health care providers and 
community specialists to play a role in clinical trials. 

Building Trust in Scientists 

Recommendation 8: Engage researchers, 
educators, and academic institutions in incorporating 
the public's perspective consistently at every level of 
training and in both the conduct of clinical research 
and the publication of findings from that research. 

Recommendation 9: Focus on educational 
strategies to help patients and communities better 
understand clinical research. This will help scientists 
because educating the public will empower and 
prepare individuals to be informed partners in the 
clinical research process. An informed and trusting 
public will enhance research participation. 

Building Trust in the NIH and Scientific 
Research 

Recommendation 10 : Continue to develop and 
fund efforts to build a national identity for the NIH 
based on what NIH does best—research and 
education—as a basis for enhancing public trust in 
clinical research. 

Recommendation 11: Review the role and impact 
of Institutional Review Boards and other patient 
protections in the clinical research process because 
the public views these protections as less effective 
than they should be. 

Recommendation 12: Document and publish 
“best practices” from efforts to reengineer the clinical 
research enterprise as soon as the NIH begins to see 
results, so that progress in improving public trust in 
medical research grows rapidly and steadily. 

Source: NIH (National Institutes of Health) (2005). Report and 
Recommendations on Public Trust in Clinical Research for the NIH 
Director from the Director's Council of Public Representatives 
(COPR). National Institutes of.Health, Director's Council of Public 
Representatives, January 14, 2005. Available: 
http://copr.nih.gov/reports/public trust.asp [accessed 12 June 2007]. 


113 








Appendix E 

List of Acronyms and Abbreviations 


AAP 

ACGIH 

AHS 

ATSDR 

BEI 

CAB 

CBPR 

CDC 

CFR 

CIOMS 

COPR 

CPSC 

CTEPP 

DEARS 

DHEW 

DMOC 

DNA 

DSMB 

DSMP 

EHCRB 

EPA 

ERG 

FCN 

FDA 

HHS 

HSRB 

HSRRO 

HUD 

ICR 

IOM 

IRB 

NAS 

NBAC 

NCI 

NCS 

NEI 

NEJAC 

NERL 


American Academy of Pediatrics 

American Conference of Governmental Industrial Hygienists 
Agricultural Health Study 

Agency for Toxic Substances and Disease Registry 
biological exposure index 
community advisory board 
community-based participatory research 
Centers for Disease Control and Prevention 
Code of Federal Regulations 

Council for International Organizations of Medical Sciences 
National Institutes of Health Director’s Council of Public Representatives 
Consumer Product Safety Commission 

Children’s Total Exposure to Persistent Pesticides and Other Persistent Organic 
Pollutants 

Detroit Exposure and Aerosol Research Study 

U.S. Department of Health, Education, and Welfare 

data monitoring and oversight committee 

deoxyribonucleic acid 

data safety monitoring board 

data and safety monitoring plan 

environmental health and community review board 

U.S. Environmental Protection Agency 

Eastern Research Group 

Federal Communicators Network 

Food and Drug Administration 

U.S. Department of Health and Human Services 

Human Studies Review Board 

Human Subjects Research Review Official 

U.S. Department of Housing and Urban Development 

information collection request 

Institute of Medicine 

institutional review board 

National Academy of Sciences 

National Bioethics Advisory Commission 

National Cancer Institute 

National Children’s Study 

National Eye Institute 

National Environmental Justice Advisory Council 
National Exposure Research Laboratory 


115 



NGO 

NHANES 

NHAPS 

NHEXAS 

NHLBI 

NHRPAC 

NIH 

NRC 

OHRP 

OMB 

OSMB 

PM 

Q&As 

QAPP 

RfD 

SEAOES 

TEAL 

TEAM 

TLV 

voc 

WHO 


Nongovernmental organization 

National Health and Nutrition Examination Survey 

National Human Activity Pattern Study 

The National Human Exposure Assessment Survey 

National Heart, Lung, and Blood Institute 

National Human Research Protections Advisory Committee 

National Institutes of Health 

National Research Council 

Office for Human Research Protections 

Office of Management and Budget 

observational study monitoring board 

particulate matter 

questions and answers 

quality assurance project plan 

reference dose 

Scientific and Ethical Approaches for Observational Exposure Studies 

Tribal Efforts Against Lead 

Total Exposure Assessment Methodology 

threshold limit value 

volatile organic compound 

World Health Organization 


116 


Appendix F 


Glossary 


Agent. A chemical, mineralogical, biological, or 
physical entity that may cause deleterious effects in an 
organism after the organism is exposed to it 
[EPA/600/Z-92/001, May 1992]. 

Assent. A child’s affirmative agreement to participate in 
research. Mere failure to object should not, absent 
affirmative agreement, be construed as assent [45 CFR 
46.402(d)], 

Autonomy. The capability' and capacity to govern 
oneself. 

Beneficence. The ethical obligation to maximize 
benefits and to minimize harms. This principle gives rise 
to norms requiring that the risks of research be 
reasonable in light of the expected benefits, that the 
research design be sound, and that the investigators be 
competent both to conduct the research and to safeguard 
the welfare of the research subjects. Beneficence further 
proscribes the deliberate infliction of harm on persons; 
this aspect of beneficence is sometimes expressed as a 
separate principle, nonmaleficence (do no harm). 

Child. A person who has not attained the age of 18 
years [40 CFR 26.202(a)] 

Collateral observations. Potentially unsafe hazards, 
conditions, or situations unrelated to the research study 
that are observed by the research staff 

Common Rule. The Common Rule is a short name for 
“The Federal Policy for the Protection of Human 
Subjects.” It was adopted by more than a dozen Federal 
departments or agencies in 1991, with EPA adapting it in 
Title 40 CFR Part 26 Subpart A. 

Community-based participatory research (CBPR). 

Collaborative research with a community in which the 
community is involved in all phases of the research. 

A fundamental concept is that the research aims to 
combine knowledge with action and to achieve social 


change to improve health outcomes and eliminate health 
disparities. 

Confidentiality. The keeping safe or not redisclosing 
by one of the parties in a confidential relationship 
information that originally was disclosed in the 
confidential relationship 

Environmental justice. The fair treatment and 
meaningful involvement of all people regardless of race, 
color, national origin, or income with respect to the 
development, implementation, and enforcement of 
environmental laws, regulations, and policies 

Exposure. Contact of a chemical, physical, or 
biological agent with the outer boundary of an organism 
(e.g., a person). Exposure is quantified as the 
concentration of the agent in the medium in contact 
integrated over the time duration of that contact. (The 
definition is taken from Guidelines for Exposure 
Assessment [EPA/600/Z-92/001, May 1992]). 

Exposure concentration. The exposure mass divided 
by the contact volume or the exposure mass divided by 
the mass of contact volume depending on the medium 

Exposure duration. The length of time over which 
continuous or intermittent contacts occur between an 
agent and a target. For example, if an individual is in 
contact with an agent for 10 minutes per day for 300 
days over a 1-year time period, the exposure duration is 
1 year. 

Exposure event. The occurrence of continuous contact 
between an agent and a target 

Exposure pathway. The course an agent takes from the 
source to the target 

Exposure route. The way an agent enters a target after 
contact (e.g., by ingestion, inhalation, or dermal 
absorption) 


117 



Human subject. A living individual about whom an 
investigator (whether professional or student) 
conducting research obtains: (1) data through 
intervention or interaction with the individual, or (2) 
identifiable private information [40 CFR 26.102(f)] 

Informed consent. A potential participant’s 
autonomous authorization to participate in the research. 
The three pillars of valid informed consent are 
(1) information, (2) comprehension, and (3) voluntary 
participation. 

Institutional review board (IRB). An IRB established 
in accord with and for the purposes expressed in EPA’s 
Policy for Protection of Subjects in Human Research 
conducted and supported by EPA [40 CFR 26.102(g)] 

Justice. The ethical obligation to treat each person in 
accordance with what is due to him or her. In the ethics 
of research involving human subjects, the principle 
refers primarily to distributive justice , which requires the 
equitable distribution of both the burdens and the 
benefits of participation in research. Differences in 
distribution of burdens and benefits are justifiable only if 
they are based on morally relevant distinctions among 
persons. 

Minimal risk. The probability and magnitude of harm 
or discomfort anticipated in the research are not greater 
in and of themselves than those ordinarily encountered 
in daily life or during the performance of routine 
physical or psychological examinations or tests [40 CFR 
26.102(i)]. 

Nonmaleficence. The proscription of deliberate 
infliction of harm on persons 

Observational human exposure study. Studies that 
involve collection of human exposure data (including 
environmental, biological, survey, activity, and various 
other forms of data) under real-world field conditions 
during normal participant day-to-day activities, with no 
additional exposures to the chemical being studied 
because of participation in the study. The studies involve 
interaction with study participants but do not involve 
intervention or manipulation of the factors being studied, 
and there is no attempt by the researcher to affect the 
outcome. 

Observational research. Any human research that does 
not meet the definition of research involving intentional 
exposure of a human subject [40 CFR 26.302] 


Privacy. Control over the extent, timing, and 
circumstances of sharing oneself (physically, 
behaviorally, or intellectually) with others 

Research. A systematic investigation, including 
research development, testing, and evaluation, designed 
to develop or contribute to generalizable knowledge 

Research involving intentional exposure of a human 
subject. A study of a substance in which the exposure 
to the substance experienced by a human subject 
participating in the study would not have occurred but 
for the human subject’s participation in the study [40 
CFR 26.202(b)] 

Respect for persons. A fundamental ethical value that 
is the basis of much of modem bioethical thought and 
regulation. The concept incorporates at least two 
fundamental ethical considerations, namely (1) respect 
for autonomy, which requires that those who are capable 
of deliberation about their personal choices should be 
treated with respect for their capacity for self- 
determination; and (2) protection of persons with 
impaired or diminished autonomy, which requires that 
those who are dependent or vulnerable be afforded 
security against harm or abuse. 

Source. The origin of an agent for the purposes of an 
exposure assessment 

Stakeholder. A person or group who has a valid 
interest in an activity, who can affect or is affected by 
the activity, and who stands to gain or lose depending on 
the decisions implemented 

Stressor. Any entity, stimulus, or condition that can 
modulate normal functions of the organism or induce an 
adverse response (e.g., agent, lack of food, drought) 

Vulnerability. A substantial incapacity to protect one’s 
own interests owing to such impediments as lack of 
capability to give informed consent, lack of alternative 
means of obtaining medical care or other expensive 
necessities, or being a junior or subordinate member of a 
hierarchical group. Accordingly, special provision must 
be made for the protection of the rights and welfare of 
vulnerable persons. 

Vulnerable groups. Populations extended additional 
human subjects protections, such as children, individuals 
with questionable capacity to consent, prisoners, fetuses 
and pregnant women, the terminally ill, students and 
employees, and comatose patients, etc. 









LC ACQUISITIONS 



111 

II19 

III! 

111 




0 

15 

6 - 

3 

62 1 




v>EPA 

United States 
Environmental Protection 
Agency 


Office of Research and Development (8101R) 
Washington, DC 20460 


Official Business 
Penalty for Private Use 
$300 



PRESORTED STANDARD 
POSTAGE & FEES PAID 
EPA 

PERMIT NO. G-35 



Recycled/Recyclable Primed on paper that contains a minimum of 
50% postconsumer fiber content processed chlorine free 


















r Arc? 


*4*^0* ° * C 0 N c * .AT 



"O ,* 

& •* *fr*^ o 



> <M oV Ul 
: 



o ya Ay * 
e V^v o 
c..r z 


£)■*{% 


v ft 




At 

Ar«? 


V ^ 


§£/■ S'-^J /\ 

v>. »n * \V 



,V° * CONC, %** * * ^/V° ’ cOHC,/<j 

_ ^ - l") ft .ru\> A M (*» -i* ^ O »i ^ rS^tV ». <t 



[O 


v/*”’ <,»**' 


tt 

O 

j. - Nxvr* .O 

? » 3S o' 3 ^p 

*♦ %. A , ' p 

* %$ 



<J>A 




jcft’ ft-'* * °Jf 

a* *VW/hV«feft «* V 

? -M&|U ° 

V * <a*^ * 

v <* 'wjijr «> <?sA 

0 , 

* <«- A -O ^S< 

Vv> ^ -f k O * frVf/7? 

ft lip*; w ? 

* ^ *fiyis? e *°** t 

A* ^ O n ** o .. 

* « * >. 0 4* ♦oho* jP t * 0 A>**n* 

^ * ^SflBto** ^p c^ fjsMflk'k ^ « 

V ° <4§P®1 r AT<? - * YV « 

** 2 

AD. % *?. ** X V. V v' « 


«*% * 

V'””W” 

^ ^«* 

V-v o 

z 



VU - 



.s^ 


ft 

>K *„W*V A 

■ »-..AV ^ Vjft ». ^ ^ <uT 

S *\* v /«fc W /| 


' ,; ^>°x * °*V*” ’VA. 
^ 



»° ^f”V 

S’ 


w 


A 0 * 
r c 


sP<i 


W 


o ^ Cy? U J> o 

* <? &K o 

* 'S' » 



o_> v-i-j x v ft J* /-, ^ 




*, Arc*?' .’ 
Z “ 

»> f5A X, 



•i »*V . •. ,%,'*■>••»’ 

r o ^ s& • • ^T ^ 

° vv u <^! ]l1 ^ r* at^ 5 - 

S‘C r . <y^> j4 






<S’ e ,o««t - ^a...,%? 

ao. «* 







a°;, . oX/‘^y, * * ^V*"-> * ..V*» •%£• * * CV'^V v *./v-n •■*>“, 

> * ' ' *' - ' * **■ * - X<? ;'i 



<v 
* 
o 
Z 

°'?x ’' :4^\ I. 

' , »b<^ 






V Ar 



o v y. 




* ^ O- 



r /*o 


° a? 

° , 

» l 

S ^^ LI ^ 




n ^c? ^jr% o 

* A? <^i o 
^ -Sr * 




c«n B< ,V ' ’ S >°^ l, A f V° ’ K V^ eO*.«*V* * ’ L 'nV 


. v* < <f A > 

V s S ^ r -V v* 

AY ^ ft -tfV. (--. 

V* o ^IABe% c.“ 






f11 * ft>" 

O ^ A^ «? 

o V AA y 

n cS'^jp o 









y va 

* V ^ 

'»* { *'n'°”'' t ^c0'<«, % 

a ao s *• 

* o >?Yk t 

K °° 0 ^ * o,. *>>***1 

# :Mfa\ %a? / 4 jfe: 

■J I" c_.r z ^-^—no.’j • 



# V ^ 


y A^ 



? 

* s> % 



* AfA 

*/W :] 

- ^ v \ 1 




* ^-v.V • • V A 


AO 


AO, 


A 



v ^ V*W/ o % +^%M2 & o O % +‘%m?2 J 

°qi a s > <o Q ^v B o, a 3 ^\o ; K**vZ*4? 

>A'”'"Av J-.s'fifr : n \ .&>'jzr*\ .#**+'.•:& :"\ vV. 


ft ft 

Gj »^ AA 
? A?a 

^ vf», « A ' 

ft v*cr * 







<r J> 


> % **0*0* ^ „ftft y.% ^N o1 ^P ,fto V»M* ^\ftft*°^ »3K0 9 A° 

Po *p r ^V s f**'v. ^ v s s A/v o* jP ? A a v. Qs> sy v 1 


• ^Po 
y -r o 

I* 4 <^ s 

v v Af>. 

.^3 * -^r^) 1 ft ”^p <A 

V » r Arv 

c 

* 




I 

ft 4' ^k j 

^ *s^ Ate 



^ vf 5 .A' . 

• r \^ : 

: J . 
* V ^ 


>° . k-X-^ c „ NO< V 4 ” '>* ^.;v*>^ c o.c, V 4 ” s > ( 

•P ^ . ft ^ t^, rP * u n J* .ft .:♦* <fL, cP . 



'o \/ 
~?r v% 



ft h n O ' Afv ^ 

“VV'-S;* 11 * 

V J « C^.CY 7* 






^ 'o.i* A’ „„„ v»’'■*••’ 

%«b /*S*A -° 

w ^ o<t 

»?v :^y». .so. 


5 »* 

4 A?.W\’I 

o,^,o, A 

—_ 


^ c qJ'*>^*lo 0 < V'w^‘V° /7 

.‘•^♦A. ^v.V'.V" \&sxi+%. \a\' 




x 



o *A^ 

^ V*v x 

» c*.o_ * 



* V X s - 

* r %<? * 
H 4 . X J 



<i V , > 

% VV u J 
r c_.n Z ^ 




09-B135 




























































































































































































































































































































































































































































































